U.S. patent number 11,097,108 [Application Number 16/840,673] was granted by the patent office on 2021-08-24 for methods and systems for lowering blood pressure through reduction of ventricle filling.
This patent grant is currently assigned to BackBeat Medical, LLC. The grantee listed for this patent is BackBeat Medical, LLC. Invention is credited to Daniel Burkhoff, Yuval Mika, Robert S. Schwartz, Darren Sherman, Robert A. Van Tassel.
United States Patent |
11,097,108 |
Mika , et al. |
August 24, 2021 |
Methods and systems for lowering blood pressure through reduction
of ventricle filling
Abstract
Systems and methods for reducing ventricle filling volume are
disclosed. In some embodiments, a stimulation circuit may be used
to stimulate a patient's heart to reduce ventricle filling volume
or even blood pressure. When the heart is stimulated at a
consistent rate to reduce blood pressure, the cardiovascular system
may over time adapt to the stimulation and revert back to the
higher blood pressure. In some embodiments, the stimulation pattern
may be configured to be inconsistent such that the adaptation
response of the heart is reduced or even prevented. In some
embodiments, a stimulation circuit may be used to stimulate a
patient's heart to cause at least a portion of an atrial
contraction to occur while the atrioventricular valve is closed.
Such an atrial contraction may deposit less blood into the
corresponding ventricle than when the atrioventricular valve is
opened throughout an atrial contraction.
Inventors: |
Mika; Yuval (Closter, NJ),
Sherman; Darren (Fort Lauderdale, FL), Schwartz; Robert
S. (Inver Grove Heights, MN), Van Tassel; Robert A.
(Excelsior, MN), Burkhoff; Daniel (Manhattan, NY) |
Applicant: |
Name |
City |
State |
Country |
Type |
BackBeat Medical, LLC |
New Hope |
PA |
US |
|
|
Assignee: |
BackBeat Medical, LLC (New
Hope, PA)
|
Family
ID: |
1000005758142 |
Appl.
No.: |
16/840,673 |
Filed: |
April 6, 2020 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20200316385 A1 |
Oct 8, 2020 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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15911249 |
Mar 5, 2018 |
10610689 |
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14652856 |
Apr 10, 2018 |
9937351 |
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PCT/US2013/076600 |
Dec 19, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61F
2/2424 (20130101); A61N 1/3682 (20130101); A61N
1/36117 (20130101); A61N 1/36564 (20130101); A61N
1/36514 (20130101); A61N 1/3684 (20130101); A61N
1/36578 (20130101); A61N 1/36528 (20130101); A61F
2/2412 (20130101); A61N 1/36585 (20130101); A61N
1/36571 (20130101); A61F 2250/0013 (20130101); A61N
1/36842 (20170801); A61N 1/36843 (20170801) |
Current International
Class: |
A61N
1/365 (20060101); A61N 1/368 (20060101); A61N
1/36 (20060101); A61F 2/24 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
2013361318 |
|
Aug 2018 |
|
AU |
|
2014367229 |
|
Jul 2019 |
|
AU |
|
2933278 |
|
Jun 2015 |
|
CA |
|
1446592 |
|
Oct 2003 |
|
CN |
|
1662278 |
|
Aug 2005 |
|
CN |
|
101309722 |
|
Nov 2008 |
|
CN |
|
101980657 |
|
Feb 2011 |
|
CN |
|
102159279 |
|
Aug 2011 |
|
CN |
|
102300603 |
|
Dec 2011 |
|
CN |
|
102551878 |
|
Jul 2012 |
|
CN |
|
106029165 |
|
Oct 2016 |
|
CN |
|
104968392 |
|
Nov 2017 |
|
CN |
|
107715299 |
|
Feb 2018 |
|
CN |
|
108025173 |
|
May 2018 |
|
CN |
|
106029165 |
|
Nov 2018 |
|
CN |
|
109219465 |
|
Jan 2019 |
|
CN |
|
109364374 |
|
Feb 2019 |
|
CN |
|
107715299 |
|
Jun 2021 |
|
CN |
|
0532148 |
|
Mar 1993 |
|
EP |
|
2241348 |
|
Oct 2010 |
|
EP |
|
2934669 |
|
Jun 2017 |
|
EP |
|
3238777 |
|
Nov 2017 |
|
EP |
|
3082949 |
|
Nov 2018 |
|
EP |
|
3461531 |
|
Apr 2019 |
|
EP |
|
3639888 |
|
Apr 2020 |
|
EP |
|
3639888 |
|
May 2021 |
|
EP |
|
1226016 |
|
Oct 2019 |
|
HK |
|
H07171218 |
|
Jul 1995 |
|
JP |
|
2002505172 |
|
Feb 2002 |
|
JP |
|
2007-519441 |
|
Jul 2007 |
|
JP |
|
2007-531609 |
|
Nov 2007 |
|
JP |
|
2010-508979 |
|
Mar 2010 |
|
JP |
|
2010-512958 |
|
Apr 2010 |
|
JP |
|
2010512855 |
|
Apr 2010 |
|
JP |
|
2010-536481 |
|
Dec 2010 |
|
JP |
|
2016501639 |
|
Jan 2016 |
|
JP |
|
2016-540589 |
|
Dec 2016 |
|
JP |
|
2018-526135 |
|
Sep 2018 |
|
JP |
|
2019-042579 |
|
Mar 2019 |
|
JP |
|
6510421 |
|
May 2019 |
|
JP |
|
2019-517842 |
|
Jun 2019 |
|
JP |
|
2019-111408 |
|
Jul 2019 |
|
JP |
|
6831087 |
|
Feb 2021 |
|
JP |
|
2021013822 |
|
Feb 2021 |
|
JP |
|
6839163 |
|
Mar 2021 |
|
JP |
|
102221586 |
|
Mar 2021 |
|
KR |
|
9944680 |
|
Sep 1999 |
|
WO |
|
9944682 |
|
Sep 1999 |
|
WO |
|
03000252 |
|
Jan 2003 |
|
WO |
|
2009035515 |
|
Mar 2005 |
|
WO |
|
2005063332 |
|
Jul 2005 |
|
WO |
|
2005097256 |
|
Oct 2005 |
|
WO |
|
2007021258 |
|
Feb 2007 |
|
WO |
|
2007044279 |
|
Apr 2007 |
|
WO |
|
2008057631 |
|
May 2008 |
|
WO |
|
2008076853 |
|
Jun 2008 |
|
WO |
|
2008079370 |
|
Jul 2008 |
|
WO |
|
2014100429 |
|
Jun 2014 |
|
WO |
|
2015094401 |
|
Jun 2015 |
|
WO |
|
2017044794 |
|
Mar 2017 |
|
WO |
|
2017184912 |
|
Oct 2017 |
|
WO |
|
Other References
Notice of Acceptance dated Jun. 5, 2020 in Australian Patent
Application No. 2018217270. cited by applicant .
Office Action dated Jun. 9, 2020 in Chinese Patent Application No.
2017109301826, and English machine translation thereof. cited by
applicant .
First Examination Report dated Jun. 22, 2020 in Australian Patent
Application No. 2019204758. cited by applicant .
Response to Office Action filed Jul. 10, 2020 in Korean Patent
Application No. 10-2015-7019640, and English machine translation
thereof. cited by applicant .
Office Action dated Jul. 30, 2020 in Japanese Patent No.
2018-238255, and English translation thereof. cited by applicant
.
Office Action dated Jul. 30, 2020 in Japanese Patent No.
2018-512118, and English translation thereof. cited by applicant
.
Arbel E.R., et al., "Successful Treatment of Drug-Resistant Atrial
Tachycardia and Intractable Congestive Heart Failure with Permanent
Coupled Atrial Pacing," Journal of the American College of
Cardiology, 1978, vol. 41 (2), pp. 336-340. cited by applicant
.
Auricchio A., et al., "Cardiac Resyncbronization Therapy Restores
Optimal Atrioventricular Mechanical Timing in Heart Failure
Patients With Ventricular Conduction Delay," Journal of the
American College of Cardiology, 2002, vol. 39 (7), pp. 1163-1169.
cited by applicant .
Auricchio A., et al., "Effect of Pacing Chamber and
Atrioventricular Delay on Acute Systolic Function of Paced Patients
With Congestive Heart Failure," Circulation--Journal of the
American Heart Association, 1999, vol. 99 (23), pp. 2993-3001.
cited by applicant .
Braunwald E., et al., "Editorial: Paired Electrical Stimulation of
the Heart: A Physiologic Riddle and a Clinical Challenge,"
Circulation, 1965, vol. 32 (5), pp. 677-681. cited by applicant
.
Calderone A., et al., "The Therapeutic Effect of Natriuretic
Peptides in Heart Failure; Differential Regulation of Endothelial
and Inducible Nitric Oxide Synthases," Heart Failure Reviews, 2003,
vol. 8 (1), pp. 55-70. cited by applicant .
U.S. Appl. No. 13/688,978, filed Nov. 29, 2012. cited by applicant
.
Han B., et al., "Cardiovascular Effects of Natriuretic Peptides and
Their Interrelation with Endothelin-1," Cardiovascular Drugs and
Therapy, 2003, vol. 17 (1), pp. 41-42. cited by applicant .
Information Manual, Model 5837 R-Wave Coupled Pulse Generator,
Prelim. Ed. III , Medtronic, 1965, 20 pages. cited by applicant
.
International Preliminary Report on Patentability for Application
No. PCT/US2005/028415, dated Feb. 21, 2008. cited by applicant
.
International Search Report and Written Opinion for Application No.
PCT/US2005/28415, dated Jan. 19, 2006. cited by applicant .
International Search Report and Written Opinion for Application No.
PCT/US2014/042777, dated Jan. 2, 2015. cited by applicant .
Invitation to Pay Additional Fees dated Oct. 17, 2014 in
International Application No. PCT/US2014/042777. cited by applicant
.
Kerwin W.F., et al., "Ventricular Contraction Abnormalities in
Dilated Cardiomyopathy: Effect of Biventricular Pacing to Correct
Interventricular Dyssynchrony," Journal of the American College of
Cardiology, 2000, vol. 35 (5), pp. 1221-1227. cited by applicant
.
Lister J.W., et al., "The Hemodynamic Effect of Slowing the Heart
Rate by Paired or Coupled Stimulation of the Atria," American Heart
Journal, 1967, vol. 73 (3), pp. 362-368. cited by applicant .
Liu L., et al., "Left Ventricular Resynchronization Therapy in a
Canine Model of Left Bundle Branch Block," American Journal of
Physiology--Heart and Circulatory Physiology, 2002, vol. 282 (6),
pp. H2238-H2244. cited by applicant .
Lopez J.F., et al., "Reducing Heart Rate of the Dog by Electrical
Stimulation," Circulation Research, 1964, vol. 15, pp. 414-429.
cited by applicant .
Nishimura K, et al., "Atrial Pacing Stimulates Secretion of Atrial
Natriuretic Polypeptide without Elevation of Atrial Pressure in
Awake Dogs with Experimental Complete Atrioventricular Block,"
Circulation Research, 1990, vol. 66 (1), pp. 115-122. cited by
applicant .
Office Action dated Jun. 4, 2015 for U.S. Appl. No. 13/957,499,
filed Aug. 2, 2013. cited by applicant .
Office Action dated May 4, 2015 for U.S. Appl. No. 13/854,283,
filed Apr. 1, 2013. cited by applicant .
Office Action dated Jun. 10, 2015 for U.S. Appl. No. 13/960,015,
filed Aug. 6, 2013. cited by applicant .
Notice of Allowance dated Dec. 16, 2014 in U.S. Appl. No.
13/826,215. cited by applicant .
O'Cochlain B., et al., "The Effect of Variation in the Interval
Between Right and Left Ventricular Activation on Paced QRS
Duration," Journal of Pacing and Clinical Electrophysiology, 2001,
vol. 24 (12), pp. 1780-1782. cited by applicant .
Office Action dated Jan. 29, 2015 for U.S. Appl. No. 13/688,978,
filed Nov. 29, 2012. cited by applicant .
Pappone C., et al., "Cardiac Pacing in Heart Failure Patients with
Left Bundle Branch Block: Impact of Pacing Site for Optimizing Left
Ventricular Resynchronization," Italian Heart Journal, 2000, vol. 1
(7), pp. 464-469. cited by applicant .
PCT Notification Concerning Transmittal of International
Preliminary Report on Patentability (IPER), International
Application No. PCT/US2005/028415, from the International Bureau
dated Feb. 21, 2008. cited by applicant .
PCT Notification of Transmittal of the International Search Report
and the Written Opinion of the International Searching Authority;
Declaration of Non-Establishment of International Search Report;
and PCT Written Opinion of International Searching Authority, dated
Apr. 24, 2014 in International Application No. PCT/US2013/076600.
cited by applicant .
Perego G.B., et al., "Simultaneous Vs. Sequential Biventricular
Pacing in Dilated Cardiomyopathy: An Acute Hemodynamic Study," The
European Journal of Heart Failure, 2003, vol. 5 (3), pp. 305-313.
cited by applicant .
Schoonderwoerd B.A., et al., "Atrial Natriuretic Peptides During
Experimental Atrial Tachycardia: Role of Developing
Tachycardiomyopathy," Journal of Cardiovascular Electrophysiology,
2004, vol. 15 (8), pp. 927-932. cited by applicant .
Siddons et al., Cardiac Pacemakers, Pub. No. 680 of American
Lecture Series, 1968, Thomas C. Publisher, pp. 200-217. cited by
applicant .
U.S. Appl. No. 13/688,978 to Levin et al., filed Nov. 29, 2012.
cited by applicant .
Verbeek X.A., et al., "Intra-Ventricular Resynchronization for
Optimal Left Ventricular Function During Pacing in Experimental
Left Bundle Branch Block," American Journal of Physiology--Heart
and Circulatory Physiology, 2003, vol. 42 (3), pp. 558-567. cited
by applicant .
Verbeek X.A., et al., "Quantification of Interventricular
Asynchrony during LBBB and Ventricular Pacing," American Journal of
Physiology--Heart and Circulatory Physiology, 2002, vol. 283 (4),
pp. H1370-H1378. cited by applicant .
Whinnett Z.I., et al., "Haemodynannic Effects of Changes in
Atrioventricular and Interventricular Delay in Cardiac
Resynchronization Therapy Show a Consistent Pattern: Analysis of
Shape, Magnitude and Relative Importance of Atrioventricular and
Interventricular Delay," Heart, 2006, vol. 92 (11), pp. 1628-1634.
cited by applicant .
Willems R., et al., "Different Patterns of Angiotensin II and
Atrial Natriuretic Peptide Secretion in a Sheep Model of Atrial
Fibrillation," Journal of the American College of Cardiology, 2001,
vol. 12 (12) , pp. 1387-1392. cited by applicant .
Zupan I., et al., "Effects of Systolic Atrial Function on Plasma
Renin Activity and Natriuretic Peptide Secretion after High Rate
Atrial and Ventricular Pacing in Dogs," Pacing and Clinical
Electrophysiology, 2005, vol. 28 (Supp 1), pp. S270-S274. cited by
applicant .
Office Action dated Jul. 13, 2015 in U.S. Appl. No. 14/642,952.
cited by applicant .
Office Action dated Aug. 14, 2015 in U.S. Appl. No. 13/688,978.
cited by applicant .
Amendment filed Oct. 9, 2015 in U.S. Appl. No. 14/642,952. cited by
applicant .
Amendment filed Oct. 16, 2015 in U.S. Appl. No. 13/854,283. cited
by applicant .
Amendment filed Nov. 5, 2015 in U.S. Appl. No. 13/688,978. cited by
applicant .
Office Action dated Nov. 4, 2015 in U.S. Appl. No. 14/427,478.
cited by applicant .
Amendment filed Nov. 30, 2015 in U.S. Appl. No. 13/957,499. cited
by applicant .
Amendment filed Dec. 3, 2015 in U.S. Appl. No. 13/960,015. cited by
applicant .
Notice of Allowance dated Dec. 18, 2015 in U.S. Appl. No.
13/854,281. cited by applicant .
Notice of Allowance dated Jan. 8, 2016 in U.S. Appl. No.
14/642,952. cited by applicant .
Amendment filed Jan. 13, 2016 in U.S. Appl. No. 14/427,478. cited
by applicant .
Final Office Action dated Jan. 20, 2016 in U.S. Appl. No.
13/960,015. cited by applicant .
Notice of Allowance dated Feb. 12, 2016 in U.S. Appl. No.
13/688,978. cited by applicant .
Notice of Allowance dated Feb. 12, 2016 in U.S. Appl. No.
14/427,478. cited by applicant .
Office Action dated Mar. 4, 2016 in U.S. Appl. No. 14/667,931.
cited by applicant .
Response to Office Action dated Dec. 10, 2020 in European Patent
Application No. 16845150.8. cited by applicant .
Final Office Action dated Dec. 14, 2020 in U.S. Appl. No.
16/359,218. cited by applicant .
Response to Office Action dated Dec. 22, 2020 in Korean Patent
Application No. 10-2016-7019183, and machine English translation
thereof. cited by applicant .
Response Second Office Action dated Jan. 25, 2021 in Canadian
Patent Application No. 2893222. cited by applicant .
Response to Second Office Action dated Jan. 27, 2021 in Chinese
Patent Application No. 2017109301826, and English translation
thereof. cited by applicant .
Notice of Allowance dated Nov. 25, 2020 in Korean Patent
Application No. 10-2015-7019640, and English translation thereof.
cited by applicant .
Examination Report dated Dec. 31, 2020 in Indian Patent Application
No. 4286/CHENP/2015. cited by applicant .
Intention to Grant dated Jan. 12, 2021 in European Patent
Application No. 19 196 148.1. cited by applicant .
Decision to Grant a Patent dated Jan. 14, 2021 in Japanese Patent
No. 2018-238255, and English translation thereof. cited by
applicant .
Certificate of Grant dated Oct. 1, 2020 in Australian Patent
Application No. 2018217270. cited by applicant .
Second Examination Report dated Oct. 1, 2020 in Australian Patent
Application No. 2019204758. cited by applicant .
Second Office Action dated Oct. 5, 2020 in Canadian Patent
Application No. 2893222. cited by applicant .
Office Action dated Oct. 23, 2020 in Korean Patent Application No.
10-2016-7019183, and English translation thereof. cited by
applicant .
Second Examination Report dated Oct. 26, 2020 in Australian Patent
Application No. 2016319787. cited by applicant .
Office Action dated Nov. 5, 2020 in European Patent Application No.
17786669.6. cited by applicant .
Office Action dated Nov. 9, 2020 in Canadian Patent Application No.
2933278. cited by applicant .
Office Action dated Nov. 13, 2020 in Chinese Patent Application No.
2017109301826, and English translation thereof. cited by applicant
.
Decision to Grant a Patent dated Nov. 26, 2020 in Japanese Patent
No. 2019-072248, and English translation thereof. cited by
applicant .
Response to First Examination Report dated Sep. 3, 2020 in
Australian Patent Application No. 2019204758. cited by applicant
.
Amendment filed Sep. 22, 2020 in U.S. Appl. No. 16/276,958. cited
by applicant .
Response to First Examination Report dated Oct. 2, 2020 in
Australian Patent Application No. 2016319787. cited by applicant
.
Response to Office Action dated Oct. 5, 2020 in Japanese Patent
Application No. 2018-512118, and English translation thereof. cited
by applicant .
Amendment filed Oct. 8, 2020 in U.S. Appl. No. 16/359,218. cited by
applicant .
Response to Office Action dated Oct. 20, 2020 in European Patent
Application No. 19 196 148.1. cited by applicant .
Response to Office Action dated Oct. 26, 2020 in Chinese Patent
Application No. 2017109301826, and English translation thereof.
cited by applicant .
Response to Office Action dated Nov. 13, 2020 in Japanese Patent
Application No. 2018-238255, and English translation thereof. cited
by applicant .
Notice of Allowance dated Nov. 19, 2020 in U.S. Appl. No.
16/276,958. cited by applicant .
Notice of Allowance dated Nov. 12, 2019 in U.S. Appl. No.
15/226,056. cited by applicant .
Response to European Office Action filed Dec. 4, 2019 in European
Patent Application No. 19196148.1. cited by applicant .
Response to Office Action filed Jun. 19, 2020 Japanese Patent No.
2019-072248, and English translation thereof. cited by applicant
.
Extended European Search Report dated Mar. 25, 2020 in European
Patent Application No. 19196148.1. cited by applicant .
Notice of Intention to Grant dated Mar. 26, 2020 in European Patent
Application No. 18205392.6. cited by applicant .
Office Action dated Apr. 28, 2020 in European Patent Application
No. 19196148.1. cited by applicant .
Response to Office Action filed May 5, 2020 in Canada Patent
Application No. 2893222. cited by applicant .
Office Action dated May 7, 2020 in Japanese Patent No. 2019-072248,
and English translation thereof. cited by applicant .
Response to Office Action filed May 12, 2020 in Japanese Patent
Application No. 2018-238255, and English translation thereof. cited
by applicant .
Office Action dated May 15, 2020 in Korean Patent No.
10-2015-7019640, and English translation thereof. cited by
applicant .
Office Action dated May 19, 2020 in Australian Patent No.
2016319787. cited by applicant .
Response to Office Action filed Jun. 3, 2020 in European Patent
Application No. 17786669.6. cited by applicant .
Office Action dated Jun. 4, 2020 in European Patent Application No.
16845150.8. cited by applicant .
Office Action dated Jun. 8, 2020 in U.S. Appl. No. 16/359,218.
cited by applicant .
Office Action dated Feb. 4, 2020 in Canada Patent Application No.
2893222. cited by applicant .
Notice of Allowance dated Sep. 27, 2019 in Hong Kong Patent
Application No. 16114537.3. cited by applicant .
Second Office Action dated Oct. 14, 2019 in Australian Patent
Application No. 2018217270. cited by applicant .
European Office Action dated Nov. 15, 2019 in European Patent
Application No. 19196148.1. cited by applicant .
Extended European Search Report dated Nov. 28, 2019 in European
Patent Application No. 17786669.6. cited by applicant .
First Office Action dated Dec. 5, 2019 in Japanese Patent
Application No. 2018-238255, and English translation thereof. cited
by applicant .
Extended European Search Report dated Jan. 21, 2019 in European
Patent Application No. 18205392.6. cited by applicant .
Decision to Grant a Patent dated Mar. 1, 2019 in Japanese Patent
Application No. 2015-549718, and English translation thereof. cited
by applicant .
Notice of Acceptance dated Mar. 22, 2019 in Australian Patent
Application No. 2014367229. cited by applicant .
Extended European Search Report dated Mar. 27, 2019 in European
Patent Application No. 16845150.8. cited by applicant .
Amendment filed Jul. 8, 2019 in U.S. Appl. No. 15/911,249. cited by
applicant .
Office Action dated Jun. 23, 2020 in U.S. Appl. No. 16/276,958.
cited by applicant .
Extended European Search Report dated Nov. 3, 2017 in European
Patent Application No. 17169068.8. cited by applicant .
Notice of Allowance dated Dec. 6, 2017 in U.S. Appl. No.
14/652,856. cited by applicant .
Supplemental Notice of Allowance dated Jan. 29, 2018 in U.S. Appl.
No. 14/652,856. cited by applicant .
Response to Examination Report filed Apr. 23, 2018 in Australian
Patent Application No. 2013361318. cited by applicant .
Amendment filed Apr. 24, 2018 in U.S. Appl. No. 15/092,737. cited
by applicant .
Notice of Allowance dated May 2, 2018 in U.S. Appl. No. 15/589,134.
cited by applicant .
Notice of Acceptance dated May 7, 2018 in Australian Patent
Application No. 2013361318. cited by applicant .
Notice of Intention to Grant dated May 7, 2018 in European Patent
Application No. 14871226.8. cited by applicant .
Office Action dated May 10, 2018 in Japanese Patent Application No.
2016-539929, and English translation thereof. cited by applicant
.
Office Action dated May 16, 2018 in U.S. Appl. No. 15/628,870.
cited by applicant .
Office Action dated May 16, 2018 in U.S. Appl. No. 15/851,787.
cited by applicant .
Response to Extended European Search Report filed May 25, 2018 in
European Patent Application No. 17 169 068.8. cited by applicant
.
Response to Office Action filed Jul. 11, 2018 in Chinese Patent
Application No. 201480075987.1, and English machine translation
thereof. cited by applicant .
Final Office Action dated Aug. 28, 2018 in Japanese Patent No.
2015-549718, and English translation thereof. cited by applicant
.
Notification Concerning Transmittal of International Preliminary
Report on Patentability (IPRP) dated Nov. 1, 2018 in International
Application No. PCT/2017/028715. cited by applicant .
Amendment filed Aug. 9, 2018 in U.S. Appl. No. 15/259,282. cited by
applicant .
Response to Office Action filed Aug. 13, 2018 in U.S. Appl. No.
15/628,870. cited by applicant .
Amendment filed Aug. 13, 2018 in U.S. Appl. No. 15/851,787. cited
by applicant .
Restriction Requirement dated Sep. 24, 2018 in U.S. Appl. No.
15/226,056. cited by applicant .
Final Office Action dated Oct. 1, 2018 in U.S. Appl. No.
15/259,282. cited by applicant .
Response to Final Office Action filed Oct. 24, 2018 in Japanese
Patent Application No. 2015-549718, with English Translation of
Amended Claims and English Machine Translation of Remarks. cited by
applicant .
Notice of Allowance dated Oct. 29, 2018 in U.S. Appl. No.
15/092,737. cited by applicant .
Response to Office Action filed Oct. 29, 2018 in Japanese Patent
Application No. 2016-539929, with English Translation of Amended
Claims and English Machine Translation of Remarks. cited by
applicant .
Notice of Allowance dated Oct. 31, 2018 in U.S. Appl. No.
15/851,787. cited by applicant .
Restriction Requirement dated Nov. 1, 2018 in U.S. Appl. No.
15/492,802. cited by applicant .
Notice of Allowance dated Nov. 26, 2018 in U.S. Appl. No.
15/628,870. cited by applicant .
Amendment and Response to Restriction Requirement filed Nov. 26,
2018 in U.S. Appl. No. 15/226,056. cited by applicant .
Response to Restriction Requirement filed Dec. 19, 2018 in U.S.
Appl. No. 15/492,802. cited by applicant .
Office Action dated Dec. 27, 2018 in U.S. Appl. No. 16/124,283.
cited by applicant .
Office Action dated Jan. 11, 2019 in U.S. Appl. No. 15/226,056.
cited by applicant .
Interview Summary dated Jan. 22, 2019 in U.S. Appl. No. 15/259,282.
cited by applicant .
Decision to Grant a Patent dated Dec. 6, 2018 in Japanese Patent
Application No. 2016-539929, with English translation thereof.
cited by applicant .
First Examination Report dated Dec. 12, 2018 in Australian Patent
Application No. 2014367229. cited by applicant .
Amendment After Final Rejection filed Feb. 1, 2019 in U.S. Appl.
No. 15/259,282. cited by applicant .
Response to Examination Report filed Feb. 22, 2019 in Australian
Patent Application No. 2014367229. cited by applicant .
Notice of Allowance dated Mar. 1, 2019 in U.S. Appl. No.
15/259,282. cited by applicant .
Office Action dated Mar. 18, 2019 in U.S. Appl. No. 15/492,802.
cited by applicant .
Notice of Allowance dated Mar. 19, 2019 in U.S. Appl. No.
15/613,344. cited by applicant .
Response to Office Action filed Mar. 27, 2019 in U.S. Appl. No.
16/124,283. cited by applicant .
Amendment Filed Apr. 10, 2019 in U.S. Appl. No. 15/266,056. cited
by applicant .
Notice of Allowance dated Jun. 5, 2019 in U.S. Appl. No.
16/124,283. cited by applicant .
Amendment filed Jun. 14, 2019 in U.S. Appl. No. 15/492,802. cited
by applicant .
Notice of Allowance dated Jul. 2, 2019 in U.S. Appl. No.
15/492,802. cited by applicant .
Notice of Intention to Grant dated May 10, 2019 in European Patent
Application No. 17169068.8. cited by applicant .
Final Office Action dated Jul. 29, 2019 in U.S. Appl. No.
15/226,056. cited by applicant .
Response to Office Action filed Sep. 9, 2019 and Sep. 18, 2019 in
European Patent Application No. 18205392.6. cited by applicant
.
First Examination Report dated Jun. 25, 2019 in Australian Patent
Application No. 2018217270. cited by applicant .
Response to First Examination Report filed Sep. 27, 2019 in
Australian Patent Application No. 2018217270. cited by applicant
.
Response to Final Office Action filed Sep. 27, 2019 in U.S. Appl.
No. 15/226,056. cited by applicant .
Response to Office Action filed Oct. 9, 2019 in European Patent
Application No. 16845150.8. cited by applicant .
Amendment filed Apr. 7, 2016 in U.S. Appl. No. 13/960,015. cited by
applicant .
Notice of Allowance dated Apr. 13, 2016 in U.S. Appl. No.
13/957,499. cited by applicant .
Advisory Action dated Apr. 18, 2016 in U.S. Appl. No. 13/960,015.
cited by applicant .
Amendment filed Jun. 6, 2016 in U.S. Appl. No. 13/960,015. cited by
applicant .
Office Action dated May 27, 2016 in European Patent Application No.
13826807.3. cited by applicant .
Office Action dated Jun. 28, 2016 in U.S. Appl. No. 15/143,742.
cited by applicant .
Office Action dated Jul. 21, 2016 in U.S. Appl. No. 13/960,015.
cited by applicant .
Amendment filed Jul. 25, 2016 in U.S. Appl. No. 14/667,931. cited
by applicant .
Office Action dated Jul. 27, 2016 in U.S. Appl. No. 15/163,078.
cited by applicant .
Notice of Allowance dated Aug. 17, 2016 in U.S. Appl. No.
14/667,931. cited by applicant .
Office Action dated Sep. 5, 2016 in Chinese Patent Application No.
201380072479.3, and English translation thereof. cited by applicant
.
Amendment filed Sep. 27, 2016 in U.S. Appl. No. 15/143,742. cited
by applicant .
Response to Office Action filed Sep. 27, 2016 in European Patent
Application No. 138268073. cited by applicant .
Amendment filed Oct. 26, 2016 in U.S. Appl. No. 15/163,078. cited
by applicant .
PCT Notification of Transmittal of the International Search Report
and the Written Opinion of the International Searching Authority;
International Search Report; and Written Opinion, dated Nov. 28,
2016 in International Application No. PCT/US2016/051023. cited by
applicant .
Notice of Intention to Grant dated Jan. 3, 2017 in European Patent
Application No. 138268073. cited by applicant .
Notice of Allowance dated Jan. 18, 2017 in U.S. Appl. No.
15/143,742. cited by applicant .
Amendment filed Jan. 19, 2017 in U.S. Appl. No. 13/960,015. cited
by applicant .
Response to Office Action filed Jan. 19, 2017 in Chinese Patent
Application No. 2013800724793, and English translation thereof.
cited by applicant .
Notice of Allowance dated Feb. 22, 2017 in U.S. Appl. No.
13/960,015. cited by applicant .
Notice of Allowance dated Mar. 15, 2017 in U.S. Appl. No.
15/163,078. cited by applicant .
Office Action dated Mar. 24, 2017 in U.S. Appl. No. 15/372,603.
cited by applicant .
Decision to Grant dated May 26, 2017 in European Patent Application
No. 138268073. cited by applicant .
Amendment filed Jun. 26, 2017 in U.S. Appl. No. 15/372,603. cited
by applicant .
Partial European Search Report dated Jul. 25, 2017 in European
Patent Application No. 17169068.8. cited by applicant .
Extended European Search Report dated Jul. 25, 2017 in European
Patent Application No. 14871226.8. cited by applicant .
Notice of Allowance dated Sep. 11, 2017 in U.S. Appl. No.
15/372,603. cited by applicant .
Office Action dated Sep. 21, 2017 in U.S. Appl. No. 15/628,870.
cited by applicant .
Office Action dated Sep. 27, 2017 in U.S. Appl. No. 15/589,134.
cited by applicant .
Office Action dated Oct. 20, 2017 in U.S. Appl. No. 15/092,737.
cited by applicant .
PCT Invitation to Pay Additional Fees dated Aug. 3, 2017 in
International Application No. PCT/US2017/028715. cited by applicant
.
Office Action dated Aug. 11, 2017 in European Patent Application
No. 14871226.8. cited by applicant .
International Search Report and Written Opinion dated Oct. 3, 2017
in International Application No. PCT/US2017/028715. cited by
applicant .
Chaliki, HP et al.; "Pulmonary Venous Pressure: Relationship to
Pulmonary Artery, Pulmonary Wedge, and Left Atrial Pressure in
Normal, Lightly Sedated Dogs"; Catheterization and Cardiovascular
Interventions; vol. 56, Issue 3; Jun. 17, 2002; p. 432, Abstract.
cited by applicant .
Office Action dated Oct. 19, 2017 in Japanese Patent Application
No. 2015-549718, and English translation thereof. cited by
applicant .
Office Action dated Nov. 6, 2017 in Australian Patent Application
No. 2013361318. cited by applicant .
Office Action dated Nov. 21, 2017 in U.S. Appl. No. 15/259,282.
cited by applicant .
Response to Restriction and Election of Species Requirement filed
Dec. 8, 2017 in U.S. Appl. No. 15/092,737. cited by applicant .
Office Action dated Dec. 27, 2017 in U.S. Appl. No. 15/092,737.
cited by applicant .
Amendment and Declaration Under 37 CFR 1.132 filed Jan. 22, 2018 in
U.S. Appl. No. 15/628,870. cited by applicant .
Amendment filed Jan. 26, 2018 in U.S. Appl. No. 15/589,134. cited
by applicant .
Response to Office Action filed Feb. 7, 2018 in European Patent
Application No. 14 871 226.8. cited by applicant .
Response to Office Action filed Feb. 21, 2018 in U.S. Appl. No.
15/259,282. cited by applicant .
Office Action dated Feb. 24, 2018 in Chinese Patent Application No.
201480075987.1, and English translation thereof. cited by applicant
.
Notification Concerning Transmittal of International Preliminary
Report on Patentability (IPRP) dated Mar. 22, 2018 in International
Application No. PCT/2016/051023. cited by applicant .
Response to Office Action filed Mar. 28, 2018 in Japanese Patent
Application No. 2015-549718, with machine English translation of
Remarks and English translation of Amended Claims. cited by
applicant .
Interview Summary dated Apr. 3, 2018 in U.S. Appl. No. 15/092,737.
cited by applicant .
Office Action dated Apr. 10, 2018 in U.S. Appl. No. 15/259,282.
cited by applicant .
Office Action dated Jun. 16, 2017 in U.S. Appl. No. 14/652,856.
cited by applicant .
Amendment filed Sep. 18, 2017 in U.S. Appl. No. 14/652,856. cited
by applicant .
Response After Final Rejection dated Feb. 24, 2021 in U.S. Appl.
No. 16/359,218. cited by applicant .
Response to Office Action dated Mar. 5, 2021 in Canadian Patent
Application No. 2933278. cited by applicant .
Response to Second Office Action dated Mar. 11, 2021 in European
Patent Application No. 17 786 669.6. cited by applicant .
Notice of Allowance dated Mar. 29, 2021 in U.S. Appl. No.
16/359,218. cited by applicant .
Response to Examiner's Report dated May 7, 2021 in Australian
Patent Application No. 2016319787. cited by applicant .
Notice of Allowance dated Mar. 3, 2021 in Chinese Patent
Application No. 2017109301826, with machine English translation
thereof. cited by applicant .
Office Action dated Mar. 29, 2021 in Chinese Patent Application No.
2016800526048, with machine English translation thereof. cited by
applicant .
Office Action dated Apr. 1, 2021 in Japanese Patent Application No.
2018-554557, with English translation thereof. cited by applicant
.
Decision of Refusal dated Apr. 8, 2021 in Japanese Patent
Application No. 2018-512118, with English translation thereof.
cited by applicant .
Decision to Grant dated Apr. 15, 2021 in European Patent
Application No. 19196148.1. cited by applicant .
Response to Office Action dated Jun. 17, 2021 in Canadian Patent
Application No. 2,893,222. cited by applicant .
Office Action dated May 12, 2021 in Korean Patent Application No.
10-2021-7005394, and English translation thereof. cited by
applicant .
Notice of Acceptance dated May 18, 2021 in Australian Patent
Application No. 2016319787. cited by applicant .
First Examination Report dated May 20, 2021 in Indian Patent
Application No. 201847042937. cited by applicant .
Notice of Intention to Grant dated May 21, 2021 in European Patent
Application No. 16 845 150.8. cited by applicant .
Notice of Intention to Grant dated Jun. 2, 2021 in European Patent
Application No. 17 786 669.6. cited by applicant .
Notice of Acceptance dated Jun. 15, 2021 in Australian Patent
Application No. 2019204758. cited by applicant.
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Primary Examiner: Morales; Jon Eric C
Attorney, Agent or Firm: Plumsea Law Group, LLC
Parent Case Text
This application is a continuation of U.S. application Ser. No.
15/911,249, filed Mar. 5, 2018, now U.S. Pat. No. 10,610,689,
issued Apr. 7, 2020, which is a continuation of U.S. application
Ser. No. 14/652,856, filed Jun. 17, 2015, now U.S. Pat. No.
9,937,351, issued Apr. 10, 2018, which is a U.S. National Stage of
International Application No. PCT/US2013/076600, filed Dec. 19,
2013, which claims priority to U.S. application Ser. No.
13/826,215, filed Mar. 14, 2013, now U.S. Pat. No. 9,008,769,
issued Apr. 14, 2015, and to U.S. Provisional Application No.
61/740,977, filed Dec. 21, 2012, all of which are herein
incorporated by reference in their entirety.
Claims
What is claimed is:
1. A method, carried out with an implanted heart muscle stimulator
associated with a heart of a patient, for treating a blood pressure
disorder in the patient, the patient having a pretreatment blood
pressure, the method comprising: determining a future anticipated
contraction of an atrium of the heart; delivering, to a ventricle
of the heart associated with the atrium, one or more stimulation
pulses a pacing time interval before the future anticipated
contraction of the atrium, such that the ventricle begins
contracting before the future anticipated contraction of the atrium
begins; and reducing blood pressure of the patient to below the
pretreatment blood pressure by at least one of reduced ventricular
filling or increased atrial stretch.
2. The method of claim 1, further comprising delivering to the
atrium one or more stimulation pulses after the pacing time
interval to cause the future anticipated contraction of the
atrium.
3. The method of claim 2, further comprising sensing atrial
excitation to confirm that the one or more stimulation pulses
delivered to the atrium are delivered before a natural excitation
of the atrium takes place.
4. The method of claim 1, further comprising allowing the future
anticipated contraction of the atrium to occur naturally without
stimulation.
5. The method of claim 1, further comprising: sensing a natural
activity rate of the atrium; and setting the pacing time interval
preceding the future anticipated contraction of the atrium based on
the sensed natural activity rate.
6. The method of claim 1, further comprising: sensing atrial
excitation to determine onset of atrial excitation; determining a
sensing delay interval as a duration from the onset of atrial
excitation to when the atrial excitation is sensed; and
determining, based on the sensing delay interval, the pacing time
interval preceding the future anticipated contraction of the
atrium.
7. The method of claim 6, wherein estimating the sensing delay
interval comprises modifying the sensing delay interval until a
resulting effect on blood pressure is equal to an effect obtained
by pacing both the atrium and the ventricle with a desired
atrioventricular delay.
8. The method of claim 1, further comprising determining the pacing
time interval by accounting for a relation between mechanical
contraction and electrical excitation of the ventricle.
9. The method of claim 1, wherein the pacing time interval is
between about 0 ms and about 50 ms.
10. The method of claim 1, wherein the atrium contracts at least
partially against a closed atrioventricular valve between the
atrium and the ventricle.
11. The method of claim 10, further comprising reducing atrial kick
by closure of the closed atrioventricular valve, thereby causing
the reduced ventricular filling.
12. The method of claim 1, wherein 100% of the future anticipated
contraction of the atrium occurs during ventricular systole of the
ventricle.
13. The method of claim 1, further comprising setting the pacing
time interval between about 0 ms and about 50 ms when an intrinsic
atrial excitation rate of the atrium is lower than an intrinsic
ventricular excitation rate of the ventricle.
14. The method of claim 1, further comprising: sensing at least one
cardiac activity parameter comprising at least one of blood
pressure, blood flow, atrioventricular valve status, or wall motion
of the heart or a part thereof; and adjusting the pacing time
interval based on the sensed at least one cardiac activity
parameter.
15. A method for reducing blood pressure of a patient, the method
comprising: delivering stimulation pulses to an atrium and a
ventricle of a heart of the patient at a first delivery rate
expected to be higher than a natural heart rate of the heart;
sensing whether a natural excitation occurs between delivery of the
stimulation pulses; when the natural excitation occurs, inhibiting
delivery of next stimulation pulses to the atrium and the
ventricle; when an amount of sensed natural excitations exceeds a
predetermined higher threshold over a given time frame, identifying
the natural heart rate as higher than the first delivery rate, and
increasing the first delivery rate to a second delivery rate that
is higher than the natural heart rate; and when an amount of sensed
natural excitations is lower than a predetermined lower threshold
over a given time frame, decreasing the first delivery rate to a
third delivery rate to avoid over-excitation of the heart.
16. The method of claim 15, further comprising sensing the natural
heart rate.
17. The method of claim 16, wherein the first delivery rate is
higher than the sensed natural heart rate of the heart, and wherein
delivering the stimulation pulses to the atrium and the ventricle
comprises stimulating the ventricle at a time between about 50 ms
before and about 70 ms after stimulation of the atrium.
18. The method of claim 15, wherein delivering the stimulation
pulses causes ventricular excitation before a stimulation pulse is
delivered to the atrium, and wherein the stimulation pulse
delivered to the atrium is delivered at a time that is earlier than
a next anticipated natural onset of atrial excitation.
19. The method of claim 15, further comprising reducing blood
pressure of the patient to below a pretreatment blood pressure by
at least one of reduced ventricular filling or increased atrial
stretch.
20. A system for treating a blood pressure disorder in a patient,
the patient having a pretreatment blood pressure, the system
comprising: a stimulation circuit configured to deliver a
stimulation pulse to at least one cardiac chamber of a heart of the
patient; and at least one controller configured to execute delivery
to a ventricle of the heart one or more stimulation pulses a pacing
time interval before a future anticipated contraction of an atrium
associated with the ventricle, such that the ventricle begins
contracting before the future anticipated contraction of the atrium
begins, thereby reducing blood pressure of the patient to below the
pretreatment blood pressure by at least one of reduced ventricular
filling or increased atrial stretch.
21. The system of claim 20, wherein the at least one controller is
further configured to deliver to the atrium one or more stimulation
pulses after the pacing time interval to cause the future
anticipated contraction of the atrium.
22. The system of claim 20, further comprising: a first sensor that
senses an excitation rate of at least one of the atrium or the
ventricle; and a second sensor that senses a parameter relating to
cardiac activity, wherein the least one controller adjusts the
pacing time interval based on the sensed parameter.
23. The system of claim 22, wherein the parameter comprises at
least one of blood pressure, blood flow, atrioventricular valve
status, or wall motion of the heart or a part thereof.
24. The system of claim 22, wherein the second sensor comprises at
least one of a pressure sensor, an impedance sensor, an ultrasound
sensor, an audio sensor, or a blood flow sensor.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
Embodiments of the present invention relate to the field of
treating hypertension through controlling cardiac filling. Specific
embodiments include application of focal, electrical stimulation to
the heart.
2. Description of Related Art
Variations in blood pressure are known to occur normally, due for
example to increased activity (which normally elevates blood
pressure) or significant blood loss (which tends to cause a
reduction in blood pressure). Blood pressure is however normally
maintained within a limited range due for example to the body's
baroreflex, whereby elevated or decreased blood pressure affects
cardiac function and the characteristics of the cardiovascular
system by a feedback loop. Such feedback control is mediated by the
nervous system as well as by the endocrine system (e.g., by
natriuretic peptide). In hypertensive individuals, while baroreflex
does function, blood pressure is maintained at an elevated
level.
Hypertension, or high blood pressure (e.g., blood pressure of
140/90 mmHg or higher), is a serious health problem affecting many
people. For example, approximately 74.5 million people aged 20
years and older and living in the United States have high blood
pressure. Hypertension may lead to such life-threatening conditions
as stroke, heart attack, and/or congestive heart failure.
Approximately 44.1% of people with high blood pressure and under
current treatment have satisfactory control of their hypertension.
Correspondingly, 55.9% of the same people have poor control.
Traditionally, treatment for hypertension has included medication
and lifestyle changes. These two types of treatment are not
effective for all patients. Additionally, side effects may prevent
certain patients from taking medication. Accordingly, there remains
a need for additional techniques for lowering blood pressure.
SUMMARY OF THE INVENTION
Methods and devices for reducing blood pressure are disclosed. Some
embodiments treat hypertension mechanically instead of or in
addition to treating hypertension pharmaceutically. In some
embodiments, an electrical stimulator, such as a pacemaker or other
type of device having a pulse generator, may be used to stimulate a
patient's heart to reduce blood pressure. When the heart is
stimulated in a consistent way to reduce blood pressure, the
cardiovascular system may adapt to the stimulation over time and
revert to a higher blood pressure. Therefore, in some embodiments,
the stimulation pattern may be configured to be able to modulate
the baroreflex such that the adaptation response of the
cardiovascular system is reduced or even prevented.
In some embodiments, an electrical stimulator may be used to
stimulate a patient's heart to cause at least a portion of an
atrial contraction to occur while the atrioventricular valve is
closed. Such an atrial contraction may deposit less blood into the
corresponding ventricle than when the atrioventricular valve is
opened during an atrial contraction.
Some embodiments may use artificial valves in treating
hypertension. In some medical conditions, where one or more of the
atrioventricular (AV) valves malfunctions, the valve(s) may be
replaced by implantation of artificial (prosthetic) valve(s). These
artificial valves may be normally configured to passively open and
close, as do natural valves, as a function of pressure differences
between the atria and ventricles. Passive artificial valves are
normally classified in three types based on their mechanical
structure: caged ball valves, tilting disc valves, and bi-leaflet
valves. As an alternative, some embodiments may use an active
artificial valve that is configured to actively open and close.
In one aspect, an embodiment provides a system for reducing blood
pressure in a patient having a pretreatment blood pressure. The
system may comprise at least one stimulation electrode for
stimulating at least one chamber of a heart of a patient with a
stimulating pulse. The system may comprise at least one controller
configured to execute a stimulation pattern of stimulating pulses
to at least a chamber of the heart. The stimulation pattern may
include a first stimulation setting and a second stimulation
setting different from the first stimulation setting. At least one
of the first stimulation setting and the second stimulation setting
may be configured to reduce or prevent atrial kick.
In one aspect, an embodiment provides a system for reducing blood
pressure. The system may comprise at least one stimulation
electrode for stimulating at least one chamber of a heart of a
patient. The system may include at least one controller configured
to execute a stimulation pattern comprising multiple stimulation
pulses. At least one stimulation pulse of the multiple stimulation
pulses may have a first stimulation setting configured to reduce
atrial kick in at least one ventricle. At least one stimulation
pulse of the multiple stimulation pulses may have a second
stimulation setting configured to reduce the baroreflex response to
the reduction in atrial kick such that the increase in blood
pressure values occurring between stimulation pulses is limited to
a predetermined value or range of values.
In another aspect, an embodiment provides a device for reducing
blood pressure of a patient having a pretreatment blood pressure
and a pretreatment ventricular filling volume. The device may
comprise a stimulation circuit configured to deliver a stimulation
pulse to at least one of an atrium and a ventricle. The device may
comprise a processor circuit coupled to the stimulation circuit and
optionally also to a sensing circuit.
In some embodiments, the device processor circuit may be configured
to operate in an operating mode in which the device controls the AV
delay, which, as used herein, may be taken to mean a delay
occurring in a single heartbeat between ventricle excitation and/or
contraction and atrial excitation and/or contraction. In addition,
as used herein, the AV delay in a system or method may be taken to
mean, within one heartbeat, a time delay between delivery of at
least one excitatory stimulus to a ventricle and one of: the
sensing of an onset of atrial excitation; the timing of an
anticipated onset of atrial excitation; and the delivery of at
least one excitatory stimulus to the atrium.
This AV delay may be set by delivering at least one stimulation
pulse to both of at least one atrium and at least one ventricle.
Optionally this stimulation is performed at a rate that is higher
than the natural activity of the heart. Such rate may, for example,
be set using at least one sensing electrode to sense the natural
activity in the heart (e.g., in the right atrium) and adjusting the
stimulation pulse delivery rate accordingly.
Optionally, when ventricular excitation is timed to commence before
the delivery of one or more stimulation pulses to the atria, the
delivery of stimulation pulses to the heart is timed such that one
or more excitatory pulses are delivered to an atrium at a time that
is earlier than the next anticipated natural onset of atrial
excitation.
In some embodiments, the AV delay may be set by delivering at least
one stimulation pulse to one or more ventricles but not to the
atria. In such case, the natural activity of one or more of the
atria may be sensed and the timing of ventricle excitation and/or
contraction may be set to precede its natural expected timing based
on the sensed atrial activity rate.
In some embodiments, the processor circuit may be configured to
operate in an operating mode in which a ventricle is stimulated to
cause ventricular excitation to commence between about 0
milliseconds (ms) and about 50 ms before the onset of atrial
excitation in at least one atrium, thereby reducing the ventricular
filling volume from the pretreatment ventricular filling volume and
reducing the patients blood pressure from the pretreatment blood
pressure. In such embodiments, atrial excitation may be sensed to
determine the onset of atrial excitation. For example, the
processor circuit may be configured to operate in an operating mode
in which one or more excitatory pulses are delivered to a ventricle
between about 0 ms and about 50 ms before a next atrial excitation
is anticipated to take place. The time interval between the onset
of atrial excitation and the moment that atrial excitation is
sensed may be known or estimated, and used to calculate the timing
of an onset of atrial excitation. For example, if it is known or
estimated that atrial excitation is sensed 5 ms after the onset of
atrial excitation and the ventricle is to be stimulated 20 ms
before the onset of atrial excitation, then the ventricle is to be
stimulated 25 ms before the next anticipated sensing of atrial
excitation. In other embodiments, the processor circuit may be
configured to operate in an operating mode in which an atrium is
stimulated to cause atrial excitation to commence between about 0
ms and about 50 ms after the onset of ventricular excitation in at
least one ventricle, thereby reducing the ventricular filling
volume from the pretreatment ventricular filling volume and
reducing the patient's blood pressure from the pretreatment blood
pressure. For example, the processor circuit may be configured to
operate in an operating mode in which one or more excitatory pulses
are delivered to an atrium between about 0 ms and about 50 ms after
one or more excitatory pulses are provided to the patient's
ventricle. In such embodiments, the pacing may be timed without
relying on sensing atrial excitation. Optionally, in such
embodiments, atrial excitation is sensed in order to confirm that
one or more excitatory pulses are delivered to an atrium before a
natural excitation takes place. Optionally, atrial excitation is
set to commence between about 0 ms and about 50 ms after the onset
of ventricular excitation when the intrinsic atrial excitation rate
is lower than the intrinsic ventricular excitation rate.
In some embodiments, the timing of the mechanical contraction in
relation to electrical excitation of a chamber for a patient may be
determined, for example, by sensing changes in atrial and
ventricular pressures, sensing wall motion using ultrasound (e.g.,
echocardiography or cardiac echo), changes in impedance, or the
opening and/or closing of a cardiac valve, using implanted and/or
external sensors as known in the art. Examples for such sensors
include pressure sensors, impedance, ultrasound sensors, and/or one
or more audio sensors and/or one or more blood flow sensors.
The timing of the mechanical contraction in relation to electrical
excitation of a chamber for a patient may be taken into account and
the processor circuit may be configured accordingly, such that the
one or more excitatory pulses are delivered to the heart in a
timing that will generate a desired pattern of contraction. This
may be performed in a closed loop mode, using one or more implanted
sensors, and/or may be performed occasionally (e.g., on
implantation of a device and/or during a checkup), for example,
using an interface with an external measurement device.
The operating mode may include stimulating the ventricle to cause
the ventricle to commence contraction before the onset of
contraction of the at least one atrium.
The operating mode may include stimulating the ventricle to cause
the ventricle to commence contraction before the end of contraction
of the at least one atrium, thereby causing the AV valve to be
closed during at least part of a contraction of the at least one
atrium.
The operating mode may include stimulating the ventricle to cause
the ventricle to commence contraction within less than 100 ms after
the onset of contraction of the at least one atrium.
Optionally, care is taken to ensure that atrial contraction will
commence before ventricle contraction has reached peak pressure.
This is possible even in cases in which ventricular contraction
will have commenced before the onset of atrial contraction, as
atrial contraction is typically faster than ventricular
contraction. Accordingly, one of the following settings may be
selected: a. The operating mode may include stimulating the
ventricle to cause the ventricle to commence contraction at any
time during atrial contraction but before the atrium reaches its
maximal contraction force. b. The operating mode may include
stimulating the ventricle to cause the ventricle to commence
contraction at any time during atrial contraction but after the
atrium reaches its maximal contraction force. c. The operating mode
may include stimulating the ventricle at such timing that
contraction would commence in both the atrium and ventricle at
essentially the same time (e.g., with no more than 5 ms from one
another), d. The operating mode may include stimulating the
ventricle to cause the ventricle to commence contraction at such
timing that the peak of atrial contraction would occur when the
ventricle is at maximal stretch, thus causing an increase in the
stretch of the atrial wall.
The operating mode may include stimulating the ventricle to cause
the ventricle to contract at least partially before the onset of
contraction of the at least one atrium, thereby causing the AV
valve to be closed during the onset of contraction of the at least
one atrium.
Optionally, the processor circuit may be configured to operate in
an operating mode in which one or more excitatory pulses are
delivered to an atrium between about 0 ms and about 50 ms after one
or more excitatory pulses are delivered to the patient's
ventricle.
In another aspect, an embodiment provides a method for reducing
blood pressure of a patient having a pretreatment blood pressure
and a pretreatment ventricular filling volume. The method may
comprise delivering a stimulation pulse from a stimulation circuit
to at least one of an atrium and a ventricle, and operating a
processor circuit coupled to the stimulation circuit to operate in
an operating mode in which a ventricle is stimulated to cause
ventricular excitation to commence between about 0 ms and about 50
ms before the onset of atrial excitation in at least one atrium,
thereby reducing the ventricular filling volume from the
pretreatment ventricular filling volume and reducing the patient's
blood pressure from the pretreatment blood pressure. In such
embodiments, atrial excitation may be sensed to determine the onset
of atrial excitation. For example, the method may include
delivering one or more excitatory pulses to a ventricle between
about 0 ms and about 50 ms before a next atrial excitation is
anticipated to take place. The time interval between the onset of
atrial excitation and the moment that atrial excitation is sensed
may be known and used to calculate the timing of the onset of
atrial excitation. For example, if it is known or estimated that
atrial excitation is sensed 5 ms after the onset of atrial
excitation and the ventricle is to be stimulated 20 ms before the
onset of atrial excitation, then the ventricle is to be stimulated
25 ms before the next anticipated sensing of atrial excitation. In
other embodiments, the method may comprise operating a processor
circuit coupled to the stimulation circuit to operate in an
operating mode in which an atrium is stimulated to cause atrial
excitation to commence between about 0 ms and about 50 ms after the
onset of ventricular excitation in at least one ventricle, thereby
reducing the ventricular filling volume from the pretreatment
ventricular filling volume and reducing the patient's blood
pressure from the pretreatment blood pressure. For example, the
method may include delivering one or more excitatory pulses to an
atrium between about 0 ms and about 50 ms after delivering one or
more excitatory pulses to the patient's ventricle. In such
embodiments, the pacing may be timed without relying on sensing
atrial excitation. Optionally, such embodiments comprise sensing
atrial excitation in order to confirm that one or more excitatory
pulses are delivered to an atrium before a natural excitation takes
place. Optionally, atrial excitation is set to commence between
about 0 ms and about 50 ms after the onset of ventricular
excitation when the intrinsic atrial excitation rate is lower than
the intrinsic ventricular excitation rate.
In some embodiments, the timing of the mechanical contraction in
relation to electrical excitation of a chamber for a patient may be
evaluated using, for example, ultrasound (e.g., echocardiography or
cardiac echo) or other known means. The timing of the mechanical
contraction in relation to electrical excitation of a chamber for a
patient may be taken into account and the timing of the delivery of
the one or more excitatory pulses to the heart may be selected so
as to generate a desired pattern of contraction.
The operating mode may include stimulating the ventricle to cause
the ventricle to contract before the onset of contraction of the at
least one atrium.
The operating mode may include stimulating the ventricle to cause
the ventricle to contract before the onset of contraction of the at
least one atrium, thereby causing the AV valve to be closed during
at least part of a contraction of the at least one atrium.
The operating mode may include stimulating the ventricle to cause
the ventricle to contract before the end of contraction of the at
least one atrium, thereby causing the AV valve to be closed during
the onset of contraction of at least atrium.
Optionally, the method comprises delivering one or more excitatory
pulses to an atrium between about 0 ms and about 50 ms after
delivering one or more excitatory pulses to the patient's
ventricle.
In another aspect, an embodiment provides a device for reducing
blood pressure of a patient having a pretreatment blood pressure
and a pretreatment ventricular filling volume. The device may
comprise a stimulation circuit configured to deliver a stimulation
pulse to at least one cardiac chamber of a patient's heart. The
device may comprise a processor circuit coupled to the stimulation
circuit. The processor circuit may be configured to operate in an
operating mode in which at least one cardiac chamber is stimulated
to cause between about 40% of an atrial contraction and about 100%
of an atrial contraction to occur at a time when an
atrioventricular valve related to the atrium is closed, thereby
reducing the ventricular filling volume from the pretreatment
ventricular filling volume and reducing the patient's blood
pressure from the pretreatment blood pressure. This can be
achieved, for example, by causing the atrium to commence
contraction about 60 ms or less before the closure of the AV valve.
Optionally, this timing may be set periodically (e.g., upon
implantation) based on data from an external sensor and/or as a
closed loop using one or more implanted sensors.
In another aspect, an embodiment provides a device for reducing
blood pressure of a patient having a pretreatment blood pressure
and a pretreatment ventricular filling volume. The device may
comprise a stimulation circuit configured to deliver a stimulation
pulse to at least one cardiac chamber. The device may comprise a
processor circuit coupled to the stimulation circuit. The processor
circuit may be configured to operate in an operating mode in which
at least one cardiac chamber is paced to cause about 50% to about
95% of an atrial contraction to occur during ventricular systole,
thereby reducing the ventricular filling volume from the
pretreatment ventricular filling volume and reducing the patient's
blood pressure from the pretreatment blood pressure. This can be
achieved, for example, by causing the atrium to commence
contraction about 50 ms to 5 ms before commencement of ventricular
contraction. Optionally, the timing of commencement of ventricular
contraction may be set according to the timing of closure of an AV
valve. Optionally, this timing may be set periodically (e.g., upon
implantation) based on data from an external sensor and/or as a
closed loop using one or more implanted sensors.
In another aspect, an embodiment provides a method, carried out
with an implanted heart muscle stimulator associated with a heart
of a patient, for treating a blood pressure disorder in the
patient, the patient having a pretreatment blood pressure. The
method may comprise stimulating a heart to cause an atrium thereof
to contract while a heart valve associated with the atrium is
closed such that the contraction distends the atrium, and the
distending atrium results in reducing the patient's blood pressure
from the pretreatment blood pressure. This can be achieved, for
example, by causing the atria to contract at a time when the
pressure in the ventricle is maximal so that the active force of
atrial contraction will increase atrial stretch above the maximal
passive stretch caused by the contraction of the associated
ventricle(s). In such cases, the timing of the maximal contraction
of the atria should coincide with the end of the isovolumic period
or during the rapid ejection period of the ventricle. Optionally,
this timing may be set periodically (e.g., upon implantation) based
on data from an external sensor and/or as a closed loop using one
or more implanted sensors.
In another aspect, an embodiment provides a system for reducing
blood pressure. The system may comprise at least one stimulation
electrode for stimulating at least one chamber of a heart of a
patient with a stimulation pattern comprising at least one
stimulation pulse. The system may include at least one controller
configured to receive input relating to the patient's blood
pressure and adjust the stimulation pattern based on said blood
pressure. For example, the input may include receiving data sensed
by one or more sensors (implanted or external) and/or receiving
data provided by a user. For example, during implantation and/or
periodic checks, a user may provide data regarding measured blood
pressure. Optionally, the system includes an input port for
receiving this input by wired and/or wireless communication from a
measuring sensor and/or a user interface. The input may comprise
data relating to blood pressure (BP) or a change in BP, which may
be measured as systolic BP (SysBP), diastolic BP, mean arterial BP,
and/or any other related BP parameter. For example, at least one
sensor may sense the pressure or changes of pressure in one or more
cardiac chambers and adjust the stimulation pattern based on the
pressure or changes in pressure. In another embodiment, the sensor
may sense the pressure in more than one chamber and adjust the
stimulation based on the relation between the pressure waveforms of
the two chambers.
The controller may be configured to adjust the stimulation pattern
by performing an adjustment process that includes adjusting a
parameter of a first stimulation setting of at least one of the at
least one stimulation pulse.
The first stimulation setting may be configured to reduce or
prevent atrial kick in at least one ventricle.
The parameter may include the adjustment of the AV delay. For
example, a natural AV delay may be a range of 120 to 200 ms between
the onset of atrial excitation and the onset of ventricular
excitation, whether occurring naturally (i.e., without the delivery
of a stimulus to the heart) or by setting the timing of the
delivery of stimuli to one or more of the atrium and ventricle.
Optionally, adjusting the AV delay means adjusting it from a normal
AV delay (of, for example, 120 ms) to a shorter AV delay (for
example, 0 to 70 ms from the onset of atrial excitation to onset of
ventricular excitation; or an AV delay of 0 to -50 ms in which the
ventricular excitation occurs before atrial excitation). In a
preferred embodiment of the invention, a stimulation setting having
an AV delay of between -50 ms to 70 ms, preferably -40 ms to 60 ms,
more preferably -50 ms to 0 or 0 to 70 ms, preferably >0 to 70
ms, is chosen to reduce or prevent atrial kick.
The stimulation pattern may be configured to cause a reduction in
blood pressure by at least a predetermined amount within about 3
sec from an application of electricity to the heart, and to
maintain a reduction in blood pressure for a time interval of at
least 1 minute. For example, a stimulation pattern may be selected
and/or adjusted based on feedback relating to one or more sensed BP
parameters.
The time interval may be at least 5 minutes.
The predetermined amount of blood pressure reduction may be 8 mmHg
or more.
The predetermined amount of blood pressure reduction may be at
least 4% of the patient's pretreatment blood pressure.
The patient's blood pressure may not exceed a predetermined average
value during the time interval by more than a predetermined
degree.
The predetermined degree may be a difference of about 8 mmHg or
less.
The controller may be configured to execute a plurality of
stimulation patterns and receive for each of the stimulation
patterns a corresponding input data relating to the patient's blood
pressure during the stimulation. The controller may be configured
to calculate for each of the plurality of stimulation patterns at
least one blood pressure variation parameter relating to the input
data. The controller may be configured to adjust the stimulation
pattern according to the blood pressure variation parameter.
The controller may be configured to adjust the stimulation pattern
to be the one with the best blood pressure variation parameter.
The best blood pressure variation parameter may be one that
displays the lowest degree of baroreflex, or the lowest degree or
rate of adaptation as detailed herein
The best blood pressure variation parameter may be one that
displays a baroreflex or degree of adaptation within a
predetermined range as detailed herein.
The at least two stimulation patterns of the plurality of
stimulation patterns may each comprise at least one stimulation
pulse having a stimulation setting configured to reduce or prevent
atrial kick in at least one ventricle. The at least two stimulation
patterns may differ one from another by the number of times or the
length of time the at least one stimulation pulse is provided in
sequence.
The plurality of stimulation patterns may differ by the number of
times or the length of time that the system is configured to elicit
a predetermined AV delay in sequence.
The at least two stimulation patterns of the plurality of
stimulation patterns may differ from another by one or more
stimulation settings included within each of the at least two
stimulation patterns.
The plurality of stimulation patterns may include a first
stimulation pattern and a second stimulation pattern executed after
the first stimulation pattern. The second stimulation pattern may
have at least one stimulation setting that was set based on an
algorithm using blood pressure variation parameters relating to the
input data of the first stimulation pattern.
The system may comprise a blood pressure sensor for providing the
input data relating to the patient's blood pressure.
The blood pressure sensor may be implantable.
The blood pressure sensor and the controller may be configured to
operate at least partially as a closed loop.
In another aspect, an embodiment provides a system for reducing
blood pressure. The system may comprise at least one stimulation
electrode for stimulating at least one chamber of a heart of a
patient with a stimulation pulse. The system may comprise a
controller. The controller may be configured to provide a first
stimulation pattern comprising at least one stimulation setting
configured to reduce or prevent atrial kick in at least one
ventricle for a first time interval and to receive a first input
data relating to a patient's blood pressure during said first time
interval. The controller may be configured to calculate at least
one blood pressure variation parameter relating to the first input
data. The controller may be configured to adjust at least one
parameter of a second stimulation pattern comprising a second
stimulation setting configured to reduce or prevent atrial kick in
at least one ventricle. The second stimulation setting may be based
upon the at least one blood pressure variation parameter. The
controller may be configured to provide the second stimulation
pattern for a second time interval.
In another aspect, an embodiment may provide a system for reducing
blood pressure. The system may comprise at least one stimulation
electrode for stimulating at least one chamber of a heart of a
patient with a stimulation pulse. The system may comprise at least
one controller configured to execute a stimulation pattern
comprising at least one stimulation setting configured to reduce or
prevent atrial kick in at least one ventricle. The stimulation
pattern may be selected to cause an immediate reduction in blood
pressure from an initial pressure value to a reduced pressure value
and to maintain a patient's average blood pressure at rest at least
8 mmHg below the initial pressure.
The reduced blood pressure value may be maintained for a time
interval of at least 1 minute.
In another aspect, an embodiment provides a kit for reducing blood
pressure. The kit may comprise at least one device for setting a
stimulation pattern for reducing blood pressure. The device may
comprise at least one stimulation electrode. The device may
comprise a controller for setting an adjustable stimulation pattern
and a set of instructions for adjusting the stimulation pattern
based on input relating to patient blood pressure.
In another aspect, an embodiment provides a system for reducing
blood pressure. The system may comprise at least one stimulation
electrode for stimulating at least one chamber of a heart of a
patient. The system may comprise at least one controller configured
to execute a stimulation pattern comprising at least one
stimulation pulse having at least one stimulation setting
configured to reduce or prevent atrial kick in at least one
ventricle. The at least one stimulation setting may be configured
such that maximum atrial stretch is at a value that is about equal
to or lower than the maximum atrial stretch of the same heart when
not receiving stimulation. Atrial stretch may be measured,
calculated, and/or estimated as known in the art. In some
embodiments, atrial stretch determination may include measuring
atrial pressure. In some embodiments, atrial stretch determination
may include measuring or estimating the dimension of an atrium
(e.g., diameter, size, or circumference).
The at least one stimulation setting may be configured to cause an
atrium to be at maximum contraction when the AV valve is open.
The at least one stimulation setting may be configured to alter the
mechanics of at least one atrial contraction such that the
mechanics of the at least one atrial contraction are different from
the mechanics of a previous natural atrial contraction. The
mechanics of atrial contraction may be assessed using any known
technique including, for example, ultrasound (e.g.,
echocardiography or cardiac echo).
The at least one stimulation setting may be configured to reduce
the force of at least one atrial contraction. The force of atrial
contraction may be reduced, for example, by temporarily generating
atrial spasm or atrial flutter. One example is the delivery of a
burst of rapid stimulation pulses to the atrium for a short period
of predefined time. The force of atrial contraction can be
calculated from sensing of atrial pressure and/or a derivative
thereof such as wall motion or flow using any known means. Such
sensing may be used as a feedback in a closed loop and/or
occasionally (e.g., upon implantation and/or checkups).
The at least one stimulation setting may be configured to prevent
at least one atrial contraction. Atrial contraction may be
prevented, for example, by temporarily generating atrial spasm or
atrial flutter. One example is the delivery of a burst of rapid
stimulation pulses to the atrium for a short period of predefined
time.
In another aspect, an embodiment provides a system for reducing
blood pressure. The system may comprise at least one stimulation
electrode for stimulating at least one chamber of a heart of a
patient. The at least one controller may be configured to execute a
stimulation pattern of stimulation pulses to the heart of a
patient. The at least one controller may be configured to receive
input relating to the patient's AV valve status. This input may be
provided by wired or wireless communication from an implanted or
external acoustic sensor or blood flow sensor and/or via a user
interface. The at least one controller may be configured to adjust
the at least one stimulation pattern based on said valve
status.
The input relating to the patient's AV valve status may be
indicative of the timing of closure of the AV valve.
The input relating to the patients AV valve status may be provided
based on a heart sound sensor.
The input relating to the patient's AV valve status may be provided
based on a blood flow sensor.
The blood flow sensor may include an implanted sensor.
The blood flow sensor may include an ultrasound sensor for sensing
blood flow through the AV valve.
The blood flow sensor and the controller may be configured to
operate at least partially as a closed loop.
The stimulation pattern may comprise at least one stimulation pulse
configured to reduce or prevent the atrial kick in at least one
ventricle.
The step of adjusting the at least one stimulation pattern may
include adjusting the AV delay of at least one stimulation
pulse.
In another aspect, an embodiment provides a system for reducing
ventricular filling volume in a patient having a pretreatment
ventricular filling volume. The system may comprise a stimulation
circuit configured to deliver a stimulation pulse to at least one
cardiac chamber. The system may comprise at least one controller
configured to execute the delivery of one or more stimulation
patterns of stimulation pulses to at least one cardiac chamber. At
least one of the stimulation pulses may have a first stimulation
setting and at least one of the stimulation pulses may have a
second stimulation setting different from the first stimulation
setting. At least one of the first stimulation setting and the
second stimulation setting may be configured to reduce or prevent
atrial kick, thereby reducing the ventricular filling volume from
the pretreatment ventricular filling volume.
The first stimulation setting and the second stimulation setting
may be configured to reduce or prevent atrial kick.
The first stimulation setting may have a different AV delay than
the AV delay of the second stimulation setting.
At least one of the one or more stimulation patterns may be
repeated at least twice in a period of one hour.
The at least one controller may be configured to execute the one or
more stimulation patterns consecutively for a time interval lasting
10 minutes or longer. The first stimulation setting may be
configured to reduce or prevent atrial kick in at least one
ventricle for at least 50% of the time interval.
The second stimulation setting may have a longer AV delay than the
first stimulation setting.
The second stimulation setting has a longer AV delay than the first
stimulation setting.
The one or more consecutive stimulation patterns may comprise at
least one stimulation pulse having the first stimulation setting
for at least about 85% of the time interval.
The time interval may be at least 30 minutes long.
The time interval may be at least one hour long.
The time interval may be at least 24 hours long.
The one or more consecutive stimulation patterns may comprise at
least one stimulation pulse having a third stimulation setting
different from the first stimulation setting and the second
stimulation setting and configured to reduce or prevent atrial kick
in at least one ventricle.
The one or more consecutive stimulation patterns may comprise at
least one stimulation pulse having a third stimulation setting
different from the first stimulation setting and the second
stimulation setting and configured not to reduce or prevent atrial
kick in at least one ventricle for less than about 50% of the time
interval.
The one or more consecutive stimulation patterns may comprise a
third stimulation configured not to reduce or prevent atrial kick
in at least one ventricle for about 20% or less of the time
interval.
The one or more stimulation patterns may comprise a sequence of
10-60 stimulation pulses having the first stimulation setting. The
first stimulation setting may be configured to reduce or prevent
atrial kick in at least one ventricle, and a sequence of 1-10
heartbeats embedded within the 10-60 stimulation pulses. The
sequence of 1-10 heartbeats may have a longer AV delay than the
first stimulation setting.
The sequence of 1-10 heartbeats may include at least one
stimulation pulse having a first stimulation setting configured to
reduce or prevent atrial kick in at least one ventricle.
The sequence of 1-10 heartbeats may include at least one
stimulation pulse having a second stimulation setting.
The sequence of 1-10 heartbeats may include a natural AV delay.
At least one heartbeat of the sequence of 1-10 heartbeats may occur
without stimulation.
The first stimulation setting may be configured to reduce atrial
kick in at least one ventricle and the second stimulation setting
may be configured to reduce the baroreflex response or adaptation
to the reduction in atrial kick such that the increase in blood
pressure values occurring between stimulation pulses is limited to
a predetermined value.
The second stimulation setting may be configured to allow an
increase in blood pressure for about 1 heartbeat to 5
heartbeats.
The stimulation pattern may include multiple stimulation pulses
having the first stimulation setting,
The stimulation pattern may include multiple stimulation pulses
having the second stimulation setting.
Between about 1% of the multiple stimulation pulses and 40% of the
multiple stimulation pulses of the stimulation pattern may have the
second stimulation setting.
The stimulation pattern may include a ratio of stimulation pulses
having the first stimulation setting to the stimulation pulses
having the second stimulation setting that corresponds to a ratio
of time constants of a response to increase and decrease in blood
pressure.
The first stimulation setting may include a first AV delay and the
second stimulation setting may include a second AV delay. The first
AV delay may be shorter than the second AV delay.
The stimulation pattern may include multiple stimulation pulses
having the first stimulation setting.
The stimulation pattern may include multiple stimulation pulses
having the second stimulation setting.
Between about 1% of the multiple stimulation pulses and 40% of the
multiple stimulation pulses of the stimulation pattern may have the
second stimulation setting.
The stimulation pattern may include a ratio of stimulation pulses
having the first stimulation setting to the stimulation pulses
having the second stimulation setting that corresponds to a ratio
of time constants of the response to increase and decrease in blood
pressure.
The stimulation pattern may include a ratio of about 8 to about 13
stimulation pulses having the first stimulation setting to about 2
to about 5 the stimulation pulses having the second stimulation
setting.
One of the first stimulation setting and the second stimulation
setting may be configured to invoke a hormonal response from the
patient's body.
In another aspect, an embodiment provides a system for reducing
ventricular filling volume of a patient having a pretreatment
ventricular filling volume. The system may comprise a stimulation
circuit configured to deliver a stimulation pulse to at least one
cardiac chamber. The system may comprise at least one controller
configured to execute the delivery of one or more stimulation
patterns of stimulation pulses to at least one cardiac chamber. At
least one of the stimulation pulses may include a setting
configured to cause a ventricular excitation to commence between
about 0 ms and about 70 ms after the onset of atrial excitation,
thereby reducing the ventricular filling volume from the
pretreatment ventricular filling volume. For example, the processor
circuit may be configured to operate in an operating mode in which
one or more excitatory pulses are delivered to the ventricle
between about 0 ms and about 70 ms after the onset of atrial
excitation in at least one atrium occurs, or between about 0 ms and
about 70 ms after one or more excitatory pulses are delivered to
the atrium.
In some embodiments, the timing of a sensed atrial excitation may
be determined by taking into account a delay between actual onset
of excitation and the sensing thereof. For example, if a sensing
delay is estimated to be 20-40 ms, and stimulation pulses are to be
delivered 0-70 ms after onset of atrial excitation, a system may be
set to deliver pulses between 40 ms before the next anticipated
sensing event to 30 ms after the next anticipated sensing event or
30 ms after the next sensing event. Likewise, if the stimulation
pulses are to be delivered to the ventricle 0-50 ms before onset of
atrial excitation, assuming the same 20-40 ms sensing delay, a
system may be set to deliver pulses between 40 ms before the next
anticipated sensing event to 90 ms before the next anticipated
sensing event. Sensing delays may be due to one or more of a
distance between the site of onset of excitation and a sensing
electrode, the level of the electrical signal, characteristics of
the sensing circuit, and the threshold set of a sensing event. The
delay may include, for example, the duration of the signal
propagation from the origin of excitation to the electrode
location, the duration related to the frequency response of the
sensing circuit, and/or the duration necessary for the signal
propagation energy to reach a level detectable by a sensing
circuit. The delay may be significant and can range, for example,
between about 5 ms to about 100 ms. One approach for estimating the
delay is to use the time difference between an AV delay measured
when both atrium and ventricle are sensed and the AV delay when the
atrium is paced and the ventricle is sensed. Other approaches may
use calculation of the amplifier response time based on the set
threshold, signal strength, and frequency content. Other approaches
may include modifying the delay used with atrial sensing until the
effect on blood pressure is the same as the effect obtained by
pacing both atrium and ventricle with the desired AV delay.
In another aspect, a system is provided for reducing ventricular
filling volume in a patient having a pretreatment ventricular
filling volume. The system may include a stimulation circuit
configured to deliver a stimulation pulse to at least one cardiac
chamber. At least one controller may be configured to execute the
delivery of one or more stimulation patterns of stimulation pulses
to at least one cardiac chamber for a time interval lasting 10
minutes or longer. At least one of the stimulation pulses may have
a first stimulation setting configured to reduce or prevent atrial
kick in at least one ventricle for at least 5 minutes of the time
interval and at least one of the stimulation pulses has a second
stimulation setting different from the first stimulation setting,
thereby reducing the ventricular filling volume from the
pretreatment ventricular filling volume.
In another aspect, a method is provided for reducing ventricular
filling in a patient having a pretreatment ventricular filling
volume. The method may include a step of delivering one or more
stimulation patterns of stimulation pulses to at least one cardiac
chamber for a time interval lasting 10 minutes or longer. At least
one of the stimulation pulses may have a first stimulation setting
configured to reduce or prevent atrial kick in at least one
ventricle for at least 5 minutes of the time interval and at least
one of the stimulation pulses has a second stimulation setting
different from the first stimulation setting.
Other systems, methods, features, and advantages of the invention
will be, or will become, apparent to one of ordinary skill in the
art upon examination of the following figures and detailed
description. It is intended that all such additional systems,
methods, features and advantages be included within this
description and this summary, be within the scope of the invention,
and be protected by the following claims.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention can be better understood with reference to the
following drawings and description. The components in the figures
are not necessarily to scale, emphasis instead being placed upon
illustrating the principles of the invention. Moreover, in the
figures, like reference numerals designate corresponding parts
throughout the different views.
FIG. 1 shows the systolic blood pressure of a hypertensive patient
receiving a stimulation signal, plotted against time;
FIG. 2 shows an enlarged view of the portion of FIG. 1 marked by
dashed rectangle A;
FIG. 3A depicts an enlarged view of the portion of FIG. 2 between
time point a and point a';
FIG. 3B depicts an enlarged view of the portion of FIG. 1 marked by
dashed rectangle A';
FIG. 4 depicts an enlarged view of the portion of FIG. 1 marked by
dashed rectangle B;
FIG. 5A depicts an enlarged view of the portion of FIG. 1 marked by
dashed rectangle C;
FIG. 5B depicts an enlarged view of the portion of FIG. 5A between
time point c and point c';
FIG. 6 shows the systolic blood pressure of a hypertensive patient
receiving a stimulation signal, plotted against time;
FIG. 7 shows the systolic blood pressure of a hypertensive patient
receiving a stimulation signal, plotted against time;
FIG. 8 is a flow chart showing an exemplary method for setting
and/or selecting a stimulation pattern;
FIG. 9 is a schematic diagram illustrating an exemplary system for
reducing blood pressure;
FIG. 10A shows a time plot including: electrocardiogram, aortic
pressure and left ventricular pressure of a healthy canine
heart;
FIG. 10B shows a time plot including: electrocardiogram, aortic
pressure and left ventricular pressure of a healthy canine
heart;
FIG. 11A shows a time plot of a hypertensive canine heart,
including right atria pressure, magnified diastolic portion of
right ventricular pressure, right ventricular pressure and
electrocardiogram;
FIG. 11B shows a time plot of a hypertensive canine heart,
including right atria pressure, magnified diastolic portion of
right ventricular pressure, right ventricular pressure and
electrocardiogram;
FIG. 12 shows a right atria pressure, magnified diastolic portion
of right ventricular pressure, right ventricular pressure, left
ventricular pressure and at the same graph aortic pressure and an
electrocardiogram of a hypertensive canine heart;
FIG. 13 is a flow chart showing an exemplary method 40 for reducing
blood pressure;
FIG. 14 is a flow chart showing an exemplary method 40 for reducing
blood pressure;
FIG. 15 is a schematic diagram illustrating an artificial valve
according to an embodiment; and
FIG. 16 shows the systolic blood pressure of a hypertensive patient
receiving a stimulation signal, plotted against time.
DETAILED DESCRIPTION
The human heart comprises two atria and two ventricles. In a normal
heart cycle, cardiac contraction begins with atrial contraction,
which is followed by contraction of the ventricles.
The mechanical process of cardiac contraction is controlled by
conduction of electricity in the heart. During each heartbeat, a
wave of depolarization is triggered by cells in the sinoatrial
node. The depolarization propagates in the atria to the
atrioventricular (AV) node and then to the ventricles. In a healthy
heart, atrioventricular delay (AV delay), i.e., the delay time
between the onset of atrial excitation and the onset of ventricular
excitation, is normally between 120 milliseconds (ms) and 200 ms.
The relative timing of the atrial contraction and the ventricular
contraction is affected inter alia by the relative timing of
excitation of each chamber and by the time needed by the chamber to
generate mechanical contraction as a result of the electrical
activation (depending on size, speed of propagation, differences in
myocyte properties, etc.).
Before contraction, the heart muscle is relaxed and blood flows
freely into the ventricles from the atria, through a valve between
them. This period can be divided into a rapid filling phase and a
slow filling phase. The rapid filling phase commences just after
the relaxation of the ventricle, during which blood from the venous
system and the atria rapidly fills the ventricle. The rapid filling
phase lasts for approximately 110 ms and is followed by the slow
filling phase, which lasts until the start of the contraction of
the atria. The duration of the slow filling phase depends on the
heart rate. Thereafter, as an atrium contracts, pressure increases
in the atrium and causes blood to flow more rapidly into the
ventricle. This contribution of atrial contraction to ventricle
filling is known as the "atrial kick." Atrial kick is normally
responsible for about 10%-30% of ventricle filling.
A cardiac cycle begins at the onset of atrial excitation. Then,
about 50-70 ms thereafter the atrium begins to contract, for a
period of about 70-110 ms. Meanwhile, the electrical stimulus
propagates to the ventricle and the onset of ventricle excitation
occurs at an AV delay of about 120-200 ms later (the AV delay can
be about 250 ms in some unhealthy individuals). As the ventricle
contracts, pressure builds up within it and passively closes the
valves between each of the atria and a respective ventricle (AV
valves), thus stopping the flow of blood from the atrium into the
ventricle and preventing backflow. During the next period of the
contraction, a period known as isovolumic contraction that lasts
approximately 50 ms, all ventricle valves are closed and the
pressure in the ventricle rapidly rises with no significant change
in volume. As ventricular pressure further increases, the valve
between the ventricle and artery opens and blood flows out of the
ventricle and away from the heart. The contraction is further
divided into a rapid ejection period and a decreased ejection
period. The rapid ejection period lasts approximately 90-110 ms,
during which about 2/3 of the stroke volume is ejected. At the end
of the rapid ejection period, the pressure in the ventricle and the
atria reaches its peak. The rapid ejection period is followed by
the decreased ejection period lasting about 130-140 ms. Thereafter,
all valves close again and the ventricle relaxes in isovolumic
relaxation for about 60-80 ms, during which the pressure in the
ventricle drops. At this time, the valves between the ventricle and
the atria reopen allowing blood to flow freely into the ventricle,
and a new excitation cycle may commence.
In the present disclosure, cardiac stimulation may be used to
reduce ventricular filling volume and/or blood pressure (BP). BP or
a change in BP may be measured as systolic BP (SysBP), diastolic
BP, mean arterial BP, BP in one or more chambers, and/or any other
related BP parameter. In some embodiments, an electrical
stimulator, such as a pacemaker or other type of device having a
pulse generator, may be used to stimulate a patient's heart to
reduce blood pressure. Electrodes electrically connected to the
electrical stimulator with a wired or wireless connection may be
placed adjacent a cardiac chamber. The electrical stimulator may be
operated to deliver a pulse to the cardiac chamber via the
electrode.
In some embodiments, stimulating the heart such that the
contribution of atrial contraction to the filling of the ventricles
(atrial kick) is reduced or even prevented, reduces cardiac filling
at the end of diastole and consequently reduces blood pressure. For
simplicity, in the following description, such stimulation will be
termed "BPR (Blood Pressure Reducing) stimulation." BPR stimulation
may include delivering at least one stimulation pulse to at least a
chamber of a heart such that atrial kick is reduced or even
prevented. Such a pulse will be referred to herein as a "BPR
stimulation pulse" or "BPR pulse" herein. As used herein, a
"stimulation pulse" may comprise a sequence of one or more
electrical pulses delivered to one or more chambers of said heart
within the timeframe of a single heartbeat. For example, in some
embodiments, a stimulation pulse may comprise one or more
electrical pulses delivered to one or more locations in a ventricle
and/or one or more electrical pulses delivered to one or more
locations in an atrium. Thus, in some embodiments, the stimulation
pulse may include a first electrical pulse delivered to an atrium
and a second electrical pulse delivered to the corresponding
ventricle. In some embodiments a stimulation pulse may include a
single pulse being delivered to a plurality of locations on one or
more chambers of the heart.
A stimulation setting means one or more parameters of one or more
stimulation pulses delivered in a single cardiac cycle. For
example, these parameters may include one or more of: power, a time
interval between electrical pulses that are included in a single
stimulation pulse (e.g., AV delay), a period of delivery with
respect to the natural rhythm of the heart, the length of a
stimulation pulse or a portion thereof, and the site of delivery
between two or more chambers and/or within a single chamber. A BPR
stimulation setting, or "BPR setting," may include a setting of one
or more BPR pulses.
A stimulation pattern may include a series of pulses having
identical stimulation settings or a stimulation pattern may include
multiple pulses each having different stimulation settings. For
example, a stimulation pattern may have one or more pulses having a
first setting and one or more pulses having a second setting that
is different from the first setting. When stating that a
stimulation pattern has a setting, it is understood that this means
a stimulation pattern may include at least one stimulation pulse
having that setting. It is also understood that, in some
embodiments a stimulation pattern may include one or more cardiac
cycles where no stimulation pulse is delivered, in which case the
pulse(s) may be viewed as being delivered at zero power. A
stimulation pattern may include a plurality of identical pulses or
a sequence of pulses including two or more different settings. Two
stimulation sequences in a pattern may differ in the order of
pulses provided within a setting. Two or more stimulation sequences
may optionally differ in their lengths (in time and/or number of
heartbeats). In some embodiments, a stimulation pattern may include
pulses having BPR settings. In some embodiments, a stimulation
pattern may include pulses that do not have BPR settings.
Examples of stimulation settings that are configured to reduce or
prevent atrial kick in at least one ventricle may include any of
the stimulation settings disclosed herein that are configured to
cause a reduction of a patients ventricular filling volume from the
pretreatment ventricular filling volume. This may be caused by
having at least part of an atrial contraction take place against a
closed AV valve. Some such examples include: a. Delivering one or
more stimulation pulses to a ventricle of a patient 0-50 ms before
the onset of excitation in an atrium of the patient. Optionally,
this delay is set based on sensing of atrial excitation.
Optionally, this includes delivering one or more stimulation pulses
to the atrium 0-50 ms after the delivery of stimulation pulses to
the ventricle. Optionally, this is performed at a rate that is
slightly higher than the natural heart rate of the patient. b.
Delivering one or more stimulation pulses to a ventricle of a
patient 0-70 ms after the onset of excitation in an atrium of the
patient. Optionally, this delay is set based on sensing of atrial
excitation. Optionally, this includes delivering one or more
stimulation pulses to the atrium 0-70 ms before the delivery of
stimulation pulses to the ventricle. Optionally, this is performed
at a rate that is slightly higher than the natural heart rate of
the patient.
Some embodiments may provide a system for reducing blood pressure
configured to deliver stimulation at a rate higher than the natural
heart rate based on sensed natural heart rate or natural
excitation. For example, the system may be configured to sense the
natural excitation between delivery of stimulation pulses and if a
natural activity is sensed, the system may be configured to inhibit
the delivery of the stimulation pulse to the chamber. If in a given
time frame the amount of sensed activations exceeds a threshold,
the natural heart rate may be regarded as higher than the rate of
delivery of the stimulation pulses, in which case the rate of
delivery may be increased, e.g., to accommodate increased heart
rate of a patient. On the other hand, if in a given time frame the
amount of sensed activations is lower than a threshold (this
threshold may be 0), the natural heart beat may be regarded as
lower than the rate of delivery of the stimulation pulses, in which
case the rate of delivery may be reduced, e.g., to avoid over
excitation of a patient's heart. To achieve this effect, according
to one embodiment, a system for reducing blood pressure may include
a sensor for sensing an excitation rate of at least one of an
atrium and a ventricle of a patient's heart, a stimulation circuit
configured to deliver stimulation pulses to an atrium and a
ventricle, and a processor circuit coupled to the stimulation
circuit. Optionally, a sensor for sensing the excitation rate of at
least one of an atrium and a ventricle may comprise an electrode
for sensing atrial excitation. The processor circuit may be
configured to detect the patient's heart rate based on the sensing
and operate in an operating mode in which a stimulation pulse is
provided to each of the at least one of an atrium and a ventricle.
The stimulation pulse may be delivered at a rate that is higher
than the sensed excitation rate and may be configured to stimulate
the ventricle at a time between about 50 ms before and about 70 ms
after stimulation of the atrium.
Reducing atrial kick may have an immediate effect on blood pressure
while hormone mediated mechanisms may take a longer period. While
some devices may be configured to have both an immediate and a
hormone mediated effect, optionally, some of the BPR settings
and/or stimulation patterns may be configured to reduce or prevent
atrial kick without a significant increase in atrial stretch. For
example, when the AV valve closes at a time that atrial contraction
is at peak pressure or thereafter, premature closure of the valve
does not increase atrial stretch. Thus, in some embodiments, a
device may be configured to cause the relative timing of atrial
excitation and ventricular excitation to be comparable with an AV
delay that is at least 40 ms long or at least 50 ms long. Atrial
stretch may be measured, calculated, and/or estimated as known in
the art. In some embodiments, atrial stretch determination may
include measuring atrial pressure. In some embodiments, atrial
stretch determination may include measuring or estimating the
dimension of an atrium (e.g., diameter, size, or
circumference).
In some embodiments, atrial kick may be reduced because the BPR
stimulation setting may be set such that atrial contraction of a
cardiac cycle is incomplete when the AV valve is open. In some
embodiments, atrial contraction may take place completely or in
part against a closed AV valve. In some embodiments atrial
contraction may be prevented or reduced in force.
In some embodiments, only one or more ventricles may be stimulated
and the stimulation pulse may be timed to have an abnormal AV delay
(e.g., 50 ms before to 120 ms after atrial excitation). In some
embodiments, a BPR stimulation setting may include the delivery of
at least one electrical pulse or stimulus to one or more atria. In
some embodiments, this at least one atrial stimulus may cause
atrial contraction. In some embodiments, the at least one atrial
stimulus may interfere with atrial contraction. In some
embodiments, the at least one atrial pulse may cause an atrial
spasm or another type of inefficient atrial contraction,
The reduction in blood pressure resulting from BPR stimulation may
be observed practically immediately upon application of the
stimulation signal (e.g., within 1 or 3 seconds (sec) or within 1,
3, or 5 heartbeats) and may reach a minimal blood pressure value
within less than 5 heartbeats from the beginning of
stimulation,
By controlling the settings of BPR stimulation, one may control the
degree to which BP is reduced. This degree is sometimes patient
specific and/or related to the precise positioning of one or more
stimulation and/or sensing electrodes in or on the heart.
Adaptation a. The inventors found that while stimulation is
maintained, blood pressure may display an adaptation pattern
wherein blood pressure increases after a time (some of which often
occurs in a short time being less than 5 minutes or even less than
a minute), and potentially reaches near pre-stimulation blood
pressure values (possibly due at least to baroreflex) or even
higher. The adaptation, at least in part, may be attributed to
changes in properties of the cardiovascular system, such as
increase in total peripheral resistance. The inventors further
found that termination of stimulation results in a quick return of
blood pressure to pre-stimulation values or even higher values, and
thereafter that the heart becomes responsive to the blood pressure
reducing stimulation signal at a degree similar to a heart that was
not so stimulated. In addition, it was found that different
stimulation patterns that comprise a plurality of BPR stimulation
settings result in different blood pressure adaptation patterns. b.
Stimulation patterns may, for example, comprise at least a first
stimulation setting and a second stimulation setting different from
the first stimulation setting, the first stimulation setting and
the second setting configured to reduce or prevent atrial kick. The
stimulation pattern may even comprise more than two different
stimulation settings. The second setting in some embodiments has a
longer AV-delay than the first setting. The second setting in some
embodiments may not be configured to reduce atrial kick.
In FIG. 1, the systolic blood pressure of a hypertensive patient
receiving a stimulation signal is plotted against time. The crosses
along the plotted line depict the peak systolic blood pressure for
every heartbeat. During approximately the first 2 plotted minutes,
no stimulation signal was delivered. As seen, the patient's initial
blood pressure was on average more than 150 mmHg. The oscillations
in blood pressure (about .+-.10 mmHg) are attributed to the
breathing cycle, as known in the art.
Then, a first stimulation pattern was applied during time interval
a-a', a second stimulation pattern was applied during time interval
b-b', and a third stimulation pattern was applied during time
interval c-c'. In between the stimulation patterns and after the
third stimulation pattern, the heart was not stimulated.
Attention is now drawn to FIG. 2, depicting an enlarged portion of
FIG. 1 marked by dashed rectangle A. During the time marked by the
dashed rectangle in FIG. 2, which corresponds with the time
interval a-a' in FIG. 1, a stimulation commenced and was delivered
to the patient's right atrium and right ventricle, such that the
atrium received a BPR stimulation signal (pulse) 2 ms before the
ventricle. Stimulation ended at the time marked a' in FIGS. 1 and
2. During the time interval a-a', the patient's systolic pressure
initially reduced to a minimal value below 110 mmHg, and then
gradually increased to intermediate values, between the initial
blood pressure and the achieved minimum. At point a', stimulation
stopped and an immediate overshoot in blood pressure was observed,
to a value above 170 mmHg. Within about a dozen heartbeats, the
blood pressure returned to its initial range.
The changes in blood pressure presented in FIGS. 1 and 2 represent,
at least in part, the cardiovascular system's response to changes
in blood pressure, known as the baroreflex. The baroreflex acts to
restore blood pressure to its pre-stimulation level by changing
cardiovascular characteristics (e.g., peripheral resistance and/or
cardiac contractility). It may be assumed that the reduction in
blood pressure that resulted from the reduction in ventricular
filling provoked a baroreflex response directed towards restoration
of the pre-stimulation blood pressure. The effect of the baroreflex
on the cardiovascular system is evident, for example, at point a'
in FIG. 2. At that point, the stimulation that affected ventricular
filling was withdrawn and blood pressure immediately exceeded
pre-stimulation blood pressure. This may be taken to indicate
baroreflex changes to the cardiovascular system (e.g., peripheral
resistance increased and contractility increased). At point a',
where stimulation stopped and blood pressure peaked, the baroreflex
responded to the increase in blood pressure by again changing one
or more characteristics of the cardiovascular system, this time in
order to lower the blood pressure to the level before the change.
As can be clearly seen, the response of the baroreflex feedback to
increase and decrease in blood pressure is asymmetric in that the
response to an increase in blood pressure is much faster than the
response to a decrease in blood pressure. Some embodiments may make
use of this asymmetry of the baroreflex to reduce or even prevent
adaptation of the reduction in blood pressure due to reduced
filling, for example, by controlling a stimulation pattern
accordingly, as detailed herein.
FIG. 3A depicts an enlarged view of the curve of FIG. 1 between
time point a and point a'. In FIG. 3A, an exponential function was
fitted to the plotted curve showing an adaptation response, the
function describing a relation between time and SysBP, and having
the following formula: P=Pi+DP(1-e.sup.-t/k)
Where P (in mmHg) denotes the systolic blood pressure, Pi (mmHg) is
a first average reduced blood pressure upon commencement of BPR
stimulation, DP (mmHg) is a constant representing the amount of
increase in pressure after the initial decline to a new steady
state level, k (sec) is a response time constant, e is the
mathematical constant, being the base of the natural logarithm, and
t (sec) is time.
In FIG. 3A, the matching function was as follows:
P=115+23(1-e.sup.-t/15.5)
Where Pi was found to be 115 mmHg, DP was 23 mmHg, and k was 15.5
sec.
FIG. 3B depicts an enlarged view of the portion of FIG. 1 marked by
dashed rectangle A'. In FIG. 3B, an exponential function was fitted
to the plotted curve showing an adaptation response to the
termination of the delivery of BPR stimulation. As seen, this
response, which manifested in a reduction of blood pressure, was
faster than the response to BPR stimulation.
In FIG. 3B, the matching function was as follows:
P=190-35(1-e.sup.-t/4.946)
Where Pi was found to be 190 mmHg, DP was -35 mmHg, and k was 4.946
sec.
As mentioned above, the baroreflex response to a reduction in blood
pressure is much slower than the baroreflex response to an increase
in blood pressure. This is indicated by the ratio of the
aforementioned time constants k (about 15 sec to about 5 sec) with
a much faster response to the increase in blood pressure. This
asymmetry in the speed of the baroreflex response may provide means
to design a stimulation pattern that generates an average reduction
in blood pressure and reduction or even prevention of adaptation.
For example, in a preferred embodiment, a stimulation pattern may
alternate between two stimulation settings in a way that the
weighted response favors the changes in the cardiovascular system
invoked by increase in blood pressure. In this embodiment, the
heart may be stimulated using a stimulation pattern having two
stimulation settings: the first setting designed to reduce
ventricular filling and thereby reduce blood pressure, and the
second setting designed to have normal ventricular filling, or at
least a higher ventricular filling, than that of the first setting.
This stimulation pattern may comprise pulses having the first
setting (BPR) delivered for a period of time that is shorter than
the time constant of the baroreflex response to the decrease in
blood pressure. In such case, adaptation may begin to manifest and
blood pressure may increase from the reduced level, but may not
reach its pre-stimulation level. The stimulation pattern may also
comprise pulses having the second setting (e.g., natural AV delay)
delivered for a period of time that is longer than the time
constant of the baroreflex response to increase in blood pressure.
In this case, full advantage may be taken of the baroreflex caused
reduction in blood pressure, and blood pressure may even return to
its level before the stimulation pattern switched to this second
setting. The weighted response of the baroreflex in such a pattern
may reduce or prevent adaptation while the average pressure may be
lower than a pre-stimulation level. The relation between the time
constants and the period of time allotted to the delivery of pulses
having different settings may determine the level of baroreflex
response that takes effect during the whole stimulation pattern.
If, for a given stimulation setting, the period of delivery is
selected to be shorter than the time constant of response, the
baroreflex may not be able to change the cardiovascular system back
to a pre-stimulation level, and if the period selected is greater
than the time constant, the baroreflex effect may be more
pronounced.
As seen in FIG. 1, at the interval between points b and b', a
second stimulation pattern was delivered. FIG. 4 depicts an
enlarged version of this portion of FIG. 1 (marked by dashed
rectangle B in FIG. 1). In the second stimulation pattern, a
sequence of 12 BPR pulses were delivered to both an atrium and a
corresponding ventricle at an AV delay of 2 ms, followed by 3
heartbeats at which only atrial stimulation and no ventricular
stimulation was artificially delivered. During these last 3
heartbeats, ventricular excitation occurred by the natural
conductance through the AV node that resulted in an AV delay of
.about.180 ms. This second stimulation pattern was repeated for the
duration of the shown time interval. In FIG. 4, the exponential
function matching the curve was found to be the following:
P=112+30(1-e.sup.-t/25.5)
As seen, Pi and also DP were comparable to the corresponding values
of the first stimulation pattern (a-a' in FIG. 3A). However, k of
the second pattern was nearly twice the time constant of the first
stimulation pattern. In this time interval, adaptation occurred at
a slower rate than in FIG. 3A, but blood pressure spiked more than
it did in FIG. 3A when the pattern switched between the stimulation
pulses. This result demonstrates that the use of a stimulation
pattern having alternating stimulation settings reduced
adaptation.
A third stimulation pattern was delivered as well, as seen in FIG.
1, between points c and c'. FIG. 5A depicts an enlarged view of the
portion of FIG. 1 marked by dashed rectangle C, which includes the
portion of the curve between point c and point c'. In the third
stimulation pattern, a sequence of 12 BPR pulses was delivered at
an AV delay of 2 ms, followed by 3 BPR pulses, each with a 120 ms
AV delay. This was repeated for the duration of the shown time
interval.
The portion of the curve of FIG. 5A that is marked by a dashed
rectangle is plotted in FIG. 5B. In FIG. 5B, an exponential
function was fitted to the plotted curve showing an adaptation
response to the delivery of the stimulation pattern of 12 BPR
pulses delivered at an AV delay of 2 ms followed by 3 BPR pulses,
each with a 120 ms AV delay.
In FIG. 5B, the matching function was as follows:
P=109.7+22.3(1-e.sup.-t/45.4)
Where Pi was found to be 109.7 mmHg, DP was 22.3 mmHg, and k was
45.4 sec. As seen, while the initial reduction in blood pressure
was comparable with the one shown in FIG. 3A (Pi=115 or 109.5), the
adaptation time constant (k) was much higher (45.4 sec v. 15.5
sec), meaning that a low blood pressure was maintained for a period
of time that is about 3 times greater than in FIG. 3A.
Attention is now drawn to FIG. 6, wherein a hypertensive patient's
heart was stimulated at a stimulation pattern having a sequence of
12 BPR pulses delivered at an AV delay of 2 ms, followed by 3 BPR
pulses, each with an 80 ms AV delay.
As seen, in this case, the adaptation rate was very low and almost
undetectable at the allotted time interval. An exponential formula
could not be matched, suggesting that the adaption was extremely
slow or did not exist.
In FIG. 7, a hypertensive patient's heart was stimulated with a
stimulation pattern having a sequence of 12 BPR pulses delivered at
an AV delay of 2 ms, followed by 3 BPR pulses, each with a 40 ms AV
delay. Stimulation commenced at point t.sub.1 and ended at point
t.sub.2. There was no measured adaptation response and the fitting
curve was in fact linear and had a fixed average reduced blood
pressure of about 112 mmHg, which is about 31 mmHg lower than the
blood pressure immediately before and after the time interval
t.sub.1-t.sub.2.
As apparent from the different stimulation patterns shown before, a
stimulation pattern comprising at least one BPR stimulation can be
set to at least approach one or more targets. For example, in some
embodiments, a stimulation pattern may be set to cause an initial
reduction in blood pressure (systolic and/or diastolic) that will
exceed a predetermined threshold or will be within a predetermined
range. In a more specific embodiment, the blood pressure may be
reduced by at least a given percentage or by at least a given
measure (e.g., 10 or 20 mmHg or even 30 mmHg) or the blood pressure
may be reduced to be within a given range (e.g., between 90 and 130
mmHg SysBP) or below a given target (e.g., 130 mmHg SysBP or less).
In some embodiments, a target may include maintaining a reduced
blood pressure for a prolonged period of time within a reduced
average range. For example, the pretreatment blood pressure may be
reduced to a predetermined average blood pressure for a period of
time or a number of heartbeats. In another embodiment, the target
may include causing a given percentage of heartbeats to be at the
reduced range/threshold. In some embodiments, the target may
include reducing blood pressure while also reducing the level of
spikes between stimulation pulses. For example, a stimulation
pattern may be used to lower the blood pressure to a constant blood
pressure for a predetermined interval of time. In some embodiments,
a stimulation pattern may be used to lower the blood pressure
without significantly influencing the cardiac output. For example,
applying intermittent BPR pulses may allow pulses with a higher (or
even full) atrial kick to occur between BPR pulses. The pulses with
a higher (or even full) atrial kick may prevent the BPR pulses from
significantly lowering the cardiac output. In another embodiment,
reducing adaptation that relates to lowering total peripheral
resistance together with reduction of blood pressure (afterload)
can positively affect cardiac output by affecting flow via the
blood system. In yet another embodiment, pacing at a higher rate
than the patient's natural rhythm may avoid a negative effect on
cardiac output that might be associated with lower stroke
volume.
In some embodiments, a time constant of the change in blood
pressure of a given pattern may be calculated and the stimulation
pattern may be set to have one or more BPR stimulation parameters
for an amount of time or number of heartbeats that are set as a
certain percentage of the calculated time constant. For example, in
FIGS. 3A and 3B, k was measured to be about 15 sec for the rate of
increase in blood pressure during delivery of a BPR pulses and
about 4.9 sec for the rate of adaptation to the termination of the
delivery of BPR pulses. In some embodiments, it may be desired to
prevent blood pressure from increasing beyond a given value, in
which case, the period of delivery of the BPR pulses may be
selected to be significantly smaller than k (e.g., 30% to 60% of
k). In this embodiment, the interval may be selected to be less
than 15 sec. Such an interval may include about 6-10 sec or about
8-14 heartbeats where the heart rate is about 80 heartbeats per
minute.
Optionally, it is desired to take advantage of the adaptation
response to the withdrawal of BPR pulses. In such case, a greater
portion of k might be applied. For example, based on FIG. 3B, a
period of 3-5 heartbeats may be selected (where k is about 4.9
sec). Thus, for example, based on FIGS. 3A and 3B, the inventors
applied the stimulation pattern of FIG. 4.
The stimulation pattern may be set, for example, to be the best of
a plurality of stimulation patterns (i.e., the one closest to a set
target parameter) and/or it may be selected as the first tested
stimulation pattern that conformed to a set target.
Embodiments of Methods for Setting and/or Selecting a Stimulation
Pattern
An exemplary method 600 for setting and/or selecting a stimulation
pattern is schematically depicted in FIG. 8. Method 600 may be
performed during implantation of a device for performing BPR
stimulation and/or periodically to adjust the device operation
parameters and/or continuously during operation. Method 600 may be
performed by system 700, described below. Accordingly, system 700
may be configured to perform any step of method 600. Similarly,
method 600 may include any steps system 700 is configured to
perform. For example, method 600 may include any of the functions
discussed below with respect to system 700. Additionally, method
600 may be performed by device 50, described below. Method 600 may
include any steps device 50 is configured to perform.
Throughout the present disclosure, the terms "first," "second," and
"third" are not meant to always imply an order of events. In some
cases, these terms are used to distinguish individual events from
one another without regard for order.
In some embodiments, step 601 may include setting a target blood
pressure value. This target may be an absolute blood pressure value
(e.g., a target blood pressure range, a target threshold of spike
value, and/or number or portion of spikes in a given timeframe), a
relative value (e.g., as compared with the pretreatment blood
pressure of the patient or as a comparison between a plurality of
tested stimulation patterns), or both. The target blood pressure
value may be a blood pressure value (e.g., measured in mmHg) and/or
a value associated with a formula calculated to match a blood
pressure measurement of a stimulation pattern, etc. This target
blood pressure value may be set before, during, and/or after the
other method steps and it may also be amended, for example, if not
reached by any tested simulation pattern.
Step 602 may include delivery of one or more stimulation patterns,
including a first stimulation pattern, to one or more chambers of a
patients heart. The first stimulation pattern may be a generic
stimulation pattern or the first stimulation pattern may already be
selected to match a given patient (e.g., when implanting a
replacement device). The first stimulation pattern may include at
least one stimulation setting configured to reduce or prevent
atrial kick in at least one ventricle for a first time
interval.
Step 603 may include sensing one or more parameters before, during,
and/or after the delivery of each of one or more stimulation
patterns (step 602). The sensed parameter(s) may comprise a blood
pressure value or a blood pressure related parameter (e.g., a
change in blood pressure). In some embodiments, the sensed
parameter(s) may comprise information relating to the timing and/or
extent of closure and/or opening of an AV valve. In some
embodiments, the sensed parameter(s) may comprise information
relating to the timing and/or rate of blood flow between an atrium
and ventricle of the heart. In some embodiments, the sensed
parameter(s) may include sensing pressure within a heart chamber
(e.g., an atria and/or ventricle). In some embodiments, sensing of
a patient's AV valve status, or position, (i.e., opened or closed)
may include sensing of heart sounds, for example, using audio
sensors. In some embodiments, sensing of a patient's AV valve
status may include Doppler sensing and/or imaging of cardiac
movement. In some embodiments, the patient's AV valve status may be
sensed by a blood flow sensor.
In some embodiments, sensing of blood flow may be performed by one
or more implanted sensors in one or more cardiac chambers. For
example, one or more pressure sensors may be placed in the right
ventricle. In some embodiments, a plurality of pressure sensors may
be placed in a plurality of chambers. Optionally, measurements of a
plurality of sensors may be combined. Optionally, pressure changes,
trends of pressure changes, and/or pressure change patterns may be
used to provide information relating to blood flow. In some
embodiments, comparing relative changes between two or more sensors
in different chambers may be used.
When a stimulation pattern is delivered to a heart (step 602), the
one or more parameters may be measured at least once during
delivery of the stimulation pattern or at a plurality of times or
even continuously. Each stimulation pattern may be delivered more
than once.
Step 604 may include analyzing the sensed parameter(s). In some
embodiments, once at least one stimulation pattern is delivered and
corresponding parameter(s) are sensed, analysis may be performed
(604). In embodiments in which multiple parameters are sensed, step
604 may include the following: comparing sensed parameter values to
a target; comparing sensed parameters between two or more
stimulation patterns; comparing calculated values (e.g., the k
constant) relating to two or more stimulation patterns; and
comparing additional sensed parameters between two or more
stimulation patterns. In some embodiments, this last function may
be performed to determine and select which stimulation pattern
yields a higher ejection fraction, stroke volume, cardiac output,
and/or a lower battery use.
Step 605 may include setting a pacing (stimulation) pattern. When
more than one parameter is sensed, the stimulation pattern used in
step 605 may be selected based on the plurality of parameters, a
plurality of target values, and/or a plurality of target
ranges.
In some embodiments, the steps shown in FIG. 8 may be performed in
the order shown by the arrows in FIG. 8. In other embodiments, the
steps may be performed in another order. For example, step 602 may
be performed before setting a target blood pressure value in
accordance with step 601. In some embodiments, a stimulation
pattern may be set to be performed indefinitely. In some
embodiments, a stimulation pattern may be set to be performed for a
predetermined period of time. For example, in some embodiments, the
stimulation pattern set during step 605 may be performed for a
predetermined period of time and then step 602, step 603, and step
604 may be repeated to determine how another stimulation pattern
affects the patient's blood pressure. Then, based on the analysis
performed in step 604, step 605 may also be repeated.
In some embodiments, method 600 may include a step of adjusting a
first stimulation pattern, thus making the first stimulation
pattern into a second stimulation pattern. In some embodiments,
step 605 of setting a stimulation pattern may include adjusting a
stimulation pattern. For example, step 605 may include adjusting a
parameter of a first stimulation setting, e.g., the time interval
from step 602. In another embodiment, step 605 may include
adjusting a parameter of a first stimulation setting configured to
reduce or prevent the atrial kick in at least one ventricle. In
some embodiments, step 605 may include adjusting first stimulation
pattern to be a second stimulation pattern configured to cause a
reduction in blood pressure by at least a predetermined amount. In
some embodiments, the predetermined amount may include, for
example, about 8 mmHg to about 30 mmHg. In some embodiments, the
predetermined amount may be at least 4% of a patient's pretreatment
blood pressure. For example, the predetermined amount may be about
4% of a patient's pretreatment blood pressure to about 30% of a
patient's pretreatment blood pressure.
In some embodiments, step 605 may include adjusting the stimulation
pattern to be a stimulation pattern configured to cause an
immediate reduction in blood pressure by at least a predetermined
amount. For example, in some embodiments, step 605 may include
adjusting the stimulation pattern to be a stimulation pattern
configured to cause a reduction in blood pressure by at least a
predetermined amount within about 3 sec from an application of
electricity to the heart. In some embodiments, step 605 may include
adjusting the stimulation pattern to be a stimulation pattern
configured to cause a reduction in blood pressure by at least a
predetermined amount within at least 5 heartbeats of the applied
electricity. In some embodiments, the reduction in blood pressure
resulting from a stimulation pattern set during step 605 may occur
within 1-3 sec of the application of electricity to the heart or
within 1, 3, or 5 heartbeats of the application of electricity to
the heart.
In some embodiments, the reduction in blood pressure resulting from
a stimulation pattern set during step 605 may be such that a
patient's average blood pressure at rest is at least 8 mmHg below
the patient's initial blood pressure at rest. In some embodiments,
the reduction in blood pressure resulting from a stimulation
pattern set during step 605 may be maintained for at least 1
minute. In some embodiments, the reduction in blood pressure
resulting from a stimulation pattern set during step 605 may be
maintained for at least 5 minutes. In some embodiments, the blood
pressure may reach a minimal blood pressure value within less than
5 heartbeats from the beginning of stimulation. For example, step
605 may include adjusting a first stimulation pattern to be a
second stimulation pattern configured to cause a reduction in blood
pressure. In some embodiments, step 605 may include adjusting the
first stimulation pattern to a second stimulation pattern
configured to cause a reduction in blood pressure for a
predetermined time interval. For example, the predetermined time
interval may include at least 1 minute or at least 5 minutes.
In some embodiments, the second stimulation pattern may be
configured to maintain a blood pressure that does not exceed a
predetermined average value during the predetermined interval by
more than a predetermined degree. For example, the predetermined
degree may be a difference of about 20 mmHg or less. In some
embodiments, the predetermined degree may be a difference of about
1 mmHg to about 8 mmHg.
In some embodiments, the second stimulation pattern may include a
second stimulation setting configured to reduce or prevent the
atrial kick in at least one ventricle. The second stimulation
setting may be based upon at least one blood pressure variation
parameter calculated from an input data sensed during application
of the first stimulation pattern.
In some embodiments, the second stimulation pattern may be
configured to reduce or limit the magnitude of spikes in blood
pressure between stimulation pulses. In some embodiments, the
spikes in blood pressure between stimulation pulses may be reduced
to a percentage of a baseline blood pressure value. For example,
the second stimulation pattern may be configured to prevent more
than an 80% increase in blood pressure between pulses. In other
words, the second stimulation pattern may be configured to prevent
the blood pressure from spiking more than about 80% between pulses.
In some embodiments, the second stimulation pattern may be
configured to prevent more than a 40% increase in blood pressure
between pulses. In some embodiments, the second stimulation pattern
may be configured to prevent a blood pressure spike of more than
about 10 mmHg to about 30 mmHg between pulses. For example, in some
embodiments, the second stimulation pattern may be configured to
prevent a blood pressure spike of more than 20 mmHg between
pulses.
In some embodiments, the second stimulation pattern may comprise
multiple stimulation pulses. At least one stimulation pulse of the
multiple stimulation pulses may have a first stimulation setting
configured to reduce atrial kick in at least one ventricle. At
least one stimulation pulse of the multiple stimulation pulses may
have a second stimulation setting configured to reduce the
baroreflex response to the reduction in atrial kick such that the
increase in blood pressure values occurring between stimulation
pulses is limited to a predetermined value. In some embodiments,
the second stimulation setting may be configured to increase blood
pressure for about 1 heartbeat to 5 heartbeats to invoke negation
of the baroreflex response. In some embodiments, the second
stimulation pattern may include multiple stimulation pulses having
the first stimulation setting and multiple stimulation pulses
having the second stimulation setting. In such embodiments, between
about 1% of the multiple stimulation pulses and 40% of the multiple
stimulation pulses of the stimulation pattern may have the second
stimulation setting. In some embodiments, the second stimulation
pattern may include multiple stimulation pulses having the first
stimulation setting and multiple stimulation pulses having the
second stimulation setting. In such embodiments, between about 1%
of the multiple stimulation pulses and 40% of the multiple
stimulation pulses of the stimulation pattern may have the second
stimulation setting. In some embodiments, the stimulation pattern
may include a ratio of stimulation pulses having the first setting
to the stimulation pulses having the second setting based on a
ratio of time constants of the response to increase and decrease in
blood pressure. For example, the ratio of stimulation pulses having
the first setting to the stimulation pulses having the second
setting may be based on a ratio of the time constants of the
changes in blood pressure resulting from each of the first setting
and the second setting. In some embodiments, the first stimulation
setting may include a first AV delay and the second stimulation
setting may include a second AV delay, the first AV delay being
shorter than the second AV delay. In some embodiments, the second
stimulation pattern may include multiple stimulation pulses having
the first stimulation setting and one or more stimulation pulses
having the second stimulation setting. In some embodiments, the
second stimulation pattern may include a ratio of about 8
stimulation pulses to about 13 stimulation pulses having the first
setting to about 2 stimulation pulses to about 5 stimulation pulses
having the second setting. In some embodiments, the second
stimulation pattern may include at least one stimulation pulse
having a stimulation setting configured to invoke a hormonal
response from the patient's body. In some embodiments, the first
stimulation pattern may include at least one stimulation pulse
having a stimulation setting configured not to invoke a hormonal
response from the patient's body. In some embodiments, the second
stimulation pattern may be applied before the first stimulation
pattern in a given sequence of stimulation patterns.
In some embodiments, method 600 may include alternating between two
or more stimulation patterns. For example, method 600 may include
alternating between two to ten stimulation patterns.
In some embodiments, the blood pressure sensor and the controller
may be configured to operate at least partially as a closed
loop.
In some embodiments, method 600 may include the controller
executing a plurality of stimulation patterns and receiving for
each of the stimulation patterns a corresponding input data
relating to a patient's blood pressure during the stimulation. The
plurality of stimulation patterns may include at least two
stimulation patterns each comprising at least one stimulation pulse
having a stimulation setting configured to reduce or prevent the
atrial kick in at least one ventricle. The at least two stimulation
patterns may differ from one another by the number of times or the
length of time the at least one stimulation pulse is provided in
sequence. The at least two stimulation patterns may differ from one
another by the number of times or the length of time a
predetermined AV delay occurs in sequence. In some embodiments, the
stimulation setting may be identical in each of the at least two
stimulation patterns. In some embodiments, the stimulation setting
may include an identical AV delay for each of the at least two
stimulation patterns. In some embodiments, the at least two
stimulation patterns may differ from one another by one or more
stimulation settings included within each of the at least two
stimulation patterns.
In some embodiments, method 600 may include the controller
calculating for each of the plurality of stimulation patterns at
least one blood pressure variation parameter relating to the input
data. Method 600 may include the controller adjusting the
stimulation pattern according to the blood pressure variation
parameter. In some embodiments, method 600 may include the
controller adjusting the stimulation pattern to be the stimulation
pattern with the best blood pressure variation parameter. For
example, the best blood pressure variation parameter may include
the blood pressure variation parameter that displays the lowest
degree of baroreflex. The best blood pressure variation parameter
may include the blood pressure variation parameter that displays a
baroreflex within a predetermined range.
In some embodiments, the second stimulation pattern may include at
least one stimulation pulse having a stimulation setting configured
to invoke a hormonal response from the patient's body, while in
some embodiments, the first stimulation pattern may include at
least one stimulation pulse having a stimulation setting configured
not to invoke a hormonal response from the patient's body.
In some embodiments, the plurality of stimulation patterns may
include a first stimulation pattern and a second stimulation
pattern executed after the first stimulation pattern. The second
stimulation pattern may have at least one stimulation setting that
was set based on an algorithm using blood pressure variation
parameters relating to the input data of the first stimulation
pattern.
Embodiments of Systems for Reducing Blood Pressure
FIG. 9 schematically depicts an exemplary system 700 for reducing
blood pressure according to some embodiments. System 700 may be a
device or may comprise a plurality of devices, optionally
associated by wire or wireless communication. The device(s) may
have multiple components disposed inside a housing and/or connected
to the housing electronically and/or by wires. As shown in FIG. 9,
a heart 701 is connected to a system 700 by one or more stimulation
electrodes 702. The stimulation electrode(s) may be configured to
stimulate at least one chamber of a heart of a patient with a
stimulation pulse. In some embodiments, multiple electrode(s) 702
may each be positioned in a different chamber of the heart. For
example, one electrode may be positioned in an atrium and another
electrode may be positioned in a ventricle. In some embodiments,
multiple electrodes 702 may be positioned in a single chamber. For
example, two electrodes may be positioned in an atrium and/or two
electrodes may be positioned in a ventricle. In some embodiments,
one electrode may be positioned in first chamber and multiple
electrodes may be positioned in a second chamber.
In the present embodiment, the electrode(s) 702 may include typical
cardiac pacemaker leads, such as the Medtronic Capsure.RTM. pacing
leads. These leads are used to connect the heart 701 to system 700.
The pacing leads may be constructed with an industry standard IS-1
BI connector at one end (reference standard ISO 5148-3:2013),
electrodes at the other end, and an insulated conductor system
between them. In some embodiments, the IS-1 BI connector is
constructed using stainless steel for the two electrode contacts
and silicone as an insulating material. Some embodiments may use
polyurethane as an insulating material.
Stimulation of one or more cardiac chambers may be accomplished by
placing a voltage between the two electrodes of the atrial or
ventricular cardiac pacing leads described above. The stimulation
circuit uses a network of transistors (e.g., MOSFETS) to charge a
capacitor to a specific programmable voltage, such as 2.0V, and
then control its connection to the electrodes for a fixed period of
programmable time, such as 0.5 ms. The same network may also manage
a discharge of any residual charge that may be accumulated on the
electrodes after stimulation is complete. The same network may
control the type of stimulation applied, such as bipolar (between
the two electrodes) or unipolar (between one electrode and the
stimulator housing).
One or more electrodes may be placed in contact with one or both
ventricles and/or one or both atria, as known in the art. Such
electrodes may be used to sense and/or deliver stimuli to the
respective cardiac chamber(s). For example, pacing electrodes can
be introduced to both ventricles, with one electrode implanted into
the right ventricle and an additional electrode placed on the left
ventricle through the coronary sinus, and with the system 700
including means to generate biventricular stimulation of both
ventricles in order to reduce dyssynchrony caused by ventricular
stimulation.
System 700 may include a controller 703. System 700 may be an
electrical stimulator including a power source 704 (e.g., a battery
as known in the art of electrical stimulators). Controller 703
and/or electrode(s) 702 may draw power from power source 704.
Optionally, the electrical stimulator of system 700 is constructed
of a hermetically sealed housing and a header. The housing may be
constructed of titanium or any other biocompatible material, and
may contain a power source 704, electronics, and a telemetry coil
or communication module 707 for communication with an external
device. The power source 704 may be an implantable grade,
hermetically sealed, primary battery. The battery chemistry may be
lithium-iodine. Other embodiments may use larger or smaller
batteries. Other embodiments may use rechargeable batteries such as
Li-ion rechargeable batteries. The electronics in some embodiments
may be constructed of standard off-the-shelf electronics (e.g.,
transistors and diodes) and/or custom electronics (e.g., ASIC).
In order to detect the onset of atrial excitation and/or
ventricular excitation, one or more sensing electrodes may be
implanted at or near a site of interest in the heart. These sensing
electrodes may be the same electrodes used for delivering pulses to
the heart or dedicated sensing electrodes. The electrical activity
may be band-pass filtered to remove unwanted noise and may conform
to an international standard for cardiac pacemakers (reference
EN45502-2-1:2003), with programmable cutoff frequencies. An
electrical circuit may be used to amplify the electrical signals
generated by a propagating activation of the cardiac chamber and to
determine the onset of activation once the electrical signals
fulfill specified criteria, for example, crossing of a predefined
threshold. The signal may, for example, be amplified, with
programmable gains, and then passed to a comparator for threshold
detection, with programmable detection thresholds in steps of 0.2
mV (atrial) and 0.4 mV (ventricle). These means of detecting
excitation may introduce a delay between the actual onset of
activation in the chamber and its detection, since the detecting
electrodes may be away from the origin of excitation and the time
it takes for the signal to fulfill the detection criteria might not
be negligible and may be in the range of 5 to 50 ms or even more.
In such cases, the timing of the onset of excitation may be
estimated based on the timing of a sensed excitation, and the
delivery of stimulation pulses would be calculated to compensate
for this delay.
Optionally, the controller 703 interfaces with an accelerometer to
measure patient activity level. This patient activity level may be
used to adjust the pacing rate and/or BPR settings and/or the
stimulation pattern based upon the patient's needs. Activity level
may also be used to control a desired level of effect on blood
pressure. For example, reduction in blood pressure may be reduced
at high levels of activity to enable better performance when an
increase in blood pressure is required. Optionally, when a patient
is inactive (e.g., when sleeping) blood pressure may reduce
naturally, in which case pacing may be adjusted in order to avoid
reducing blood pressure below a desired threshold. Activity level
may also be used to adjust settings based on baroreflex to allow
better response when needed. The sensor may be, for example, a
piezoelectric sensor. Other embodiments may use a MEMS-based
accelerometer sensor. Other embodiments may use a minute
ventilation sensor, optionally in combination with an
accelerometer.
Controller 703 may be configured to deliver electricity to the
heart 701 via one or more electrodes 702. Controller 703 may be
configured to execute a stimulation pattern of stimulation pulses
according to any embodiment of this disclosure. In some
embodiments, the stimulation pulses may be delivered to at least a
ventricle of the heart. In some embodiments, the stimulation
pattern may include a first stimulation setting and a second
stimulation setting different from the first stimulation setting,
with the first stimulation setting and the second setting
configured to reduce or prevent the atrial kick. In some
embodiments, the first stimulation setting has a different AV delay
than the second stimulation setting. In some embodiments, the first
stimulation setting and/or the second stimulation setting may be
configured such that maximum atrial stretch is at a value that is
about equal to or lower than the maximum atrial stretch of the same
heart when not receiving stimulation. In some embodiments, the
first stimulation setting and/or second stimulation setting are
configured to cause an atrium to be at maximum force when the AV
valve is open. In some embodiments, the first stimulation setting
and/or second stimulation setting are configured to alter the
mechanics of at least one atrial contraction such that the
mechanics of the at least one atrial contraction are different from
the mechanics of a previous natural atrial contraction. In some
embodiments, the first stimulation setting and/or second
stimulation setting are configured to reduce the force of at least
one atrial contraction. In some embodiments, the first stimulation
setting and/or second stimulation setting are configured to prevent
at least one atrial contraction.
In some embodiments, the controller 703 may be configured to
deliver a variety of different AV delays. The controller 703 may be
configured to sense when the atrial contraction or excitation
occurs (as described herein) and then deliver ventricular
stimulation a fixed interval after that or before a future
anticipated atrial excitation or contraction. The interval may be
programmable. The controller 703 may also be configured to
stimulate the atrium and then deliver ventricular stimulation at a
fixed interval after that, which may also be programmable. The
programmable interval may, for example, be changed between 2 ms and
70 ms to accommodate a desired therapeutic effect or even provide a
negative AV delay of up to -50 ms.
In some embodiments, controller 703 may be configured to repeat a
stimulation pattern multiple times. For example, controller 703 may
repeat a stimulation pattern twice. In another embodiment,
controller 703 may be configured to repeat a stimulation pattern at
least twice in a period of an hour. The stimulation pattern
repeated by controller 703 may include any type of stimulation
pattern. For example, the stimulation pattern may include a
stimulation setting configured to reduce or prevent the atrial kick
in at least one ventricle. In another embodiment, the stimulation
pattern may include two different stimulation settings each
configured to reduce or prevent the atrial kick in at least one
ventricle. These two stimulation settings may differ by one or more
parameters, for example, by AV delay.
In some embodiments, controller 703 may be configured to execute
one or more consecutive stimulation patterns for a predetermined
time interval. For example, in some embodiments, the time interval
may be 10 minutes or longer. In another embodiment, the time
interval may be 30 minutes or longer, one hour or longer, or 24
hours or longer. In some embodiments, the time interval may be a
period of months, such as one month to one year. In some
embodiments, the time interval may be longer than one year. In some
embodiments, the one or more consecutive stimulation patterns may
include a first stimulation setting configured to reduce or prevent
the atrial kick in at least one ventricle for a portion of the time
interval. For example, the one or more consecutive stimulation
patterns may include a first stimulation setting configured to
reduce or prevent the atrial kick in at least one ventricle for
about 50% of a time interval to about 100% of the time interval. In
another embodiment, the one or more consecutive stimulation
patterns may include a first stimulation setting configured to
reduce or prevent the atrial kick in at least one ventricle for
about 50% of a time interval to about 85% of the time interval. In
some embodiments, the one or more consecutive stimulation patterns
may include a second stimulation setting having a longer AV delay
than the first stimulation setting for at least one heartbeat
during the time interval. In some embodiments, the one or more
consecutive stimulation patterns may include a second stimulation
setting and/or a third stimulation setting. The second stimulation
setting and/or third stimulation setting may each be different from
the first stimulation setting. In some embodiments, the second
stimulation setting and/or third stimulation setting may each be
configured to reduce or prevent the atrial kick in at least one
ventricle. In some embodiments, the second stimulation setting
and/or third stimulation setting may each be configured not to
reduce or prevent the atrial kick in at least one ventricle. In
some embodiments, the second stimulation setting and/or third
stimulation setting may include about 0% of a time interval to
about 50% of the time interval. In some embodiments, the second
stimulation setting and/or third stimulation setting may include
about 0% of a time interval to about 30% of the time interval. In
some embodiments, the second stimulation setting and/or third
stimulation setting may include about 0% of a time interval to
about 20% of the time interval. In some embodiments, the second
stimulation setting and/or third stimulation setting may include
about 5% of a time interval to about 20% of the time interval.
In some embodiments, controller 703 may be configured to execute
one or more consecutive stimulation patterns including a sequence
of 10-60 stimulation pulses having a first stimulation setting
configured to reduce or prevent the atrial kick in at least one
ventricle. In some embodiments, controller 703 may be configured to
execute one or more consecutive stimulation patterns including a
sequence of 1-10 heartbeats embedded within the 10-60 stimulation
pulses and the sequence of 1-10 heartbeats may have a longer AV
delay than the first stimulation setting. For example, the 10-60
stimulation pulses may include 5 stimulation pulses having the
first stimulation setting, followed by one heartbeat having a
longer AV delay than the first stimulation setting, followed by 50
stimulation pulses having the first stimulation setting. The
sequence of 1-10 heartbeats may include at least one stimulation
pulse having a first stimulation setting configured to reduce or
prevent the atrial kick in at least one ventricle. The sequence of
1-10 heartbeats may include a natural AV delay. The sequence of
1-10 heartbeats may occur without stimulation.
System 700 may further comprise one or more sensors 705. In some
embodiments, such sensor(s) 705 may include one or more sensing
electrode(s) for sensing electrical activity of the heart. In some
embodiments, one or more sensing electrode(s) may include one or
more stimulation electrode(s) 702. In some embodiments, sensor(s)
705 may include one or more blood pressure sensors (implantable
and/or external). In some embodiments, one or more sensors 705 may
include one or more pressure sensors implanted in the heart (e.g.,
in the atria and/or ventricle). In some embodiments, sensor(s) 705
may include one or more blood flow sensors (implantable and/or
external). For example, one or more sensors 705 may include
ultrasound sensing of blood flow through the AV valve. In some
embodiments, sensor(s) 705 may include one or more sensors
configured to monitor the timing of closure of the AV valve. One or
more of these sensors may be configured to operate as a closed loop
with the controller.
Information from sensor(s) 705 may be provided to controller 703 by
any form of communication, including wired communication and/or
wireless communication. Optionally, system 700 may comprise one or
more communication modules 707 for receiving and/or transmitting
information between system components and/or to devices that are
external to the system. In some embodiments, controller 703 may be
configured to receive input data relating to the patient's blood
pressure. For example, the input data relating to the patient's
blood pressure may include data indicative of BP measured at one or
more points in time or of a variation in BP (e.g. a degree of
change and/or a rate of change or a function describing the change
of blood pressure over time) and/or statistical data relating to BP
or variation in BP, maximum and/or minimum BP values
Optionally, system 700 may comprise one or more user interfaces 708
for providing information and/or for allowing input of information.
Providing information may include, for example, a display of
operational information relating to the system and/or data that was
recorded by the system and/or received by the system during
operation. This may include sensed parameter(s) and/or a relation
between sensed parameter(s) and operational information (such as
stimulation pattern settings and/or relative timing between
delivery of a given pace and sensed information).
Optionally, user interface 708 may be comprised of a commercially
available laptop computer (e.g., Windows.RTM.-based computer)
running a software application. The software application may serve
to generate orders to be delivered to an interface that is, in
turn, connected to a hand-held wand that contains a telemetry
circuit for communication with the implantable stimulator. The
orders sent to the wand may be used to set stimulation parameters
and/or to retrieve device diagnostics, device data, cardiac data,
and real-time cardiac sensing. The interface also allows for
connection of a 3-lead ECG and this data is displayed on the laptop
computer screen by the software application. Other embodiments may
not include the 3-lead ECG circuitry or may include 12-lead ECG
circuitry. Other embodiments may incorporate the functionality of
the wand, interface, and laptop computer into a dedicated piece of
hardware that performs all three functions. Other embodiments may
also add printing capability to the user interface 708.
In some embodiments, interface(s) 708 may be configured such that a
user (e.g., medical practitioner) may provide a set of control
instructions to the system (e.g., target values and/or ranges
and/or other limitations or instructions). Optionally, interface(s)
708 may allow a user to input data from one or more sensors 705
(e.g., the results of a manual blood pressure measurement and/or
results of an ultrasound monitor).
Optionally, the one or more user interfaces 708 may allow a user to
select a stimulation pattern (for example, from a set of
stimulation patterns stored in system 700) or impose constraints on
the setting and/or selecting of a stimulation pattern.
Optionally, system 700 may comprise one or more processors 706.
Processor(s) may be configured to process sensed parameters from
sensor(s) 705 and/or input data from user interface(s) 708 to
select a stimulation pattern for delivery by system 700.
Optionally, processor(s) 706 may be configured to analyze sensed
parameters and extract information and/or formula constants to be
used in the selection and/or evaluation of stimulation
patterns.
One or more components of system 700 or portions of such components
may be implanted in the patient, while some components of system
700 or portions of such components may be external to the patient.
When some components (or component parts) are implanted and others
are not, communication between the components may take place by
wired and/or wireless means, essentially as known in the art. For
example, some or all functions of both controller 703 and/or
processor 706 may be performed outside the body. Having some
components of system 700 external to the patient's body may assist
in reducing the size and/or energy requirements of an implanted
device, and/or in the enhancement of the system's computation
capabilities.
System 700 may include additional functions relating to control of
heart function and overall cardiovascular system performance. For
example, system 700 may include one or more algorithms and/or
electrodes to enable biventricular pacing or resynchronization
therapy to reduce dyssynchrony that may be caused by ventricular
stimulation. In some embodiments, system 700 may include one or
more algorithms to compensate for a possible reduction in cardiac
output. Such an algorithm that may change heart rate in order to
increase cardiac output or implement other methods known in the art
for controlling cardiac output. In some embodiments, system 700 may
include rate response algorithms to affect changes in heart rate as
a response to certain circumstances. For example, system 700 may
include rate response algorithms to affect changes in heart rate as
a response to changes in level of exercise, ventilation activity,
and/or oxygen consumption. In some embodiments, system 700 may
include a sensor that detects activity and the algorithm may turn
off stimulation while a patient is exercising such that a patient's
blood pressure is not reduced. In some embodiments, system 700 may
include a real-time clock. Such a clock may be used to control the
timing of the stimulation. For example, system 700 may include an
algorithm that turns stimulation on and off depending upon the time
of day. This type of algorithm may be used to prevent hypotension
during the night when a patient is sleeping.
In some embodiments, a kit including one or more components of
system 700 and a set of instructions for adjusting the stimulation
pattern based on input relating to a patient's blood pressure may
be provided.
Some embodiments may provide a system for reducing blood pressure
configured to deliver stimulation at a rate higher than the natural
heart rate based on sensed natural heart rate or natural
excitation. For example, the system may be configured to sense the
natural excitation between delivery of stimulation pulses and if a
natural activity is sensed, the system may be configured to inhibit
the delivery of the stimulation pulse to the chamber. If in a given
time frame the amount of sensed activations exceeds a threshold,
the natural heart rate may be regarded as higher than the rate of
delivery of the stimulation pulses, in which case the rate of
delivery may be increased, e.g., to accommodate increased heart
rate of a patient. On the other hand, if in a given time frame the
amount of sensed activations is lower than a threshold (this
threshold may be 0), the natural heart beat may be regarded as
lower than the rate of delivery of the stimulation pulses, in which
case the rate of delivery may be reduced, e.g., to avoid over
excitation of a patient's heart. To achieve this effect, according
to one embodiment, a system for reducing blood pressure may include
a sensor for sensing an excitation rate of at least one of an
atrium and a ventricle of a patient's heart, a stimulation circuit
configured to deliver stimulation pulses to an atrium and a
ventricle, and a processor circuit coupled to the stimulation
circuit. The processor circuit may be configured to detect the
patient's heart rate based on the sensing and operate in an
operating mode in which a stimulation pulse is provided to each of
the at least one of an atrium and a ventricle. The stimulation
pulse may be delivered at a rate that is higher than the sensed
excitation rate and may be configured to stimulate the ventricle at
a time between about 50 ms before and about 70 ms after stimulation
of the atrium.
Some embodiments may provide a system for reducing blood pressure
based on a predicted next atrial contraction. For example, a system
for reducing blood pressure may include a sensor for sensing an
excitation rate of at least one of an atrium and a ventricle, a
stimulation circuit configured to deliver a stimulation pulse to at
least one of an atrium and a ventricle, and a processor circuit
coupled to the stimulation circuit. The processor circuit may be
configured to operate in an operating mode in which a timing of a
next atrial excitation is predicted based on the sensed excitation
rate of the previous atrial excitations, and at least one ventricle
is stimulated at a time between about 50 ms before and about 10 ms
after the predicted next atrial excitation. The predicted timing
may be based on the time interval between the two previous sensed
atrial excitations and on a function that will be based on
previously sensed time intervals between atrial excitations. The
function may include the change in time interval, the rate of
change in time intervals, and/or detection of periodic variations
in time intervals (e.g., periodic variation due to breathing).
Optionally, a sensor for sensing the excitation rate of at least
one of an atrium and a ventricle may comprise an electrode for
sensing atrial excitation.
In a further aspect, prediction of a next atrial contraction may be
based on a function of previous sensed excitations including rate
of change of intervals and periodic variations.
In a further aspect, the timing of the predicted next atrial
excitation may be adjusted to reflect a delay between an atrial
excitation and a sensing of the atrial excitation.
In a further aspect, the system may further comprise an additional
sensor for sensing a parameter relating to cardiac activity and for
adjusting the time at which the ventricle is stimulated
accordingly. The parameter may be a member of a group consisting of
data relating to blood pressure, blood flow, AV valve status, and
wall motion of the heart or a part thereof. The additional sensor
may be selected from the group consisting of pressure sensors,
impedance sensors, ultrasound sensors, and/or one or more audio
sensors and/or one or more blood flow sensors. The additional
sensor may be implantable.
Reducing Atrial Kick
Some embodiments stem from the inventors realization that blood
pressure can be reduced by causing a closure of at least one AV
valve during at least part of an atrial contraction. This will
reduce, or even prevent, the contribution of the contraction of the
atria to the filling of the ventricles, and thus reduce cardiac
filling at the end of diastole and consequently reduce blood
pressure.
In some embodiments, at least part of an atrial contraction may
occur against a closed AV valve. For example, in some embodiments,
40% or more of an atrial contraction may occur against a closed AV
valve. In some embodiments, at least 80% of an atrial contraction
may occur against a closed AV valve. For example the contraction
may start approximately 20 ms or less before the contraction of the
ventricle or the excitation of the atria may occur 20 ms or less
before the excitation of the ventricle. In some embodiments, 100%
of an atrial contraction may occur against a closed AV valve, in
which case ventricle excitation is timed such that ventricle
contraction will begin before the commencement of atrial
contraction. This may include exciting the ventricle before the
onset of atrial excitation. The higher the percentage is of an
atrial contraction that occurs with the AV valve closed, the more
the atrial kick is reduced. Stimulation of both the atrium and the
ventricle may provide better control of the percentage of an atrial
contraction occurring against a closed valve. Various embodiments
may be implemented to cause at least part of an atrial contraction
to occur against a closed valve. For example, the AV valve may be
closed 70 ms or less after the onset of mechanical contraction of
the atrium or 40 ms or less after the onset of mechanical
contraction of the atrium or even 5 or 10 ms or less after the
onset of mechanical contraction of the atrium. In some embodiments,
the AV valve may be closed before the onset of mechanical
contraction of the atrium. For example, the AV valve may be closed
within 5 ms before the onset of the mechanical contraction of the
atrium. In some embodiments, the AV valve may be closed at the same
time as the onset of the mechanical contraction. In some
embodiments, the AV valve may be closed after the onset of the
mechanical contraction of the atrium. For example, the AV valve may
be closed within 5 ms after the onset of mechanical contraction of
the atrium.
In some embodiments, the onset of a contraction of a chamber may be
sensed and a stimulation pulse may be timed relative to the sensed
onset of a contraction. The onset of contraction in a chamber is
the start of active generation of contractile force in the chamber.
The onset of contraction can be sensed by a rapid change in
pressure that is not related to the flow of blood into the chamber.
The onset of contraction may also be sensed by measuring the
movement of the walls of a cardiac chamber or measuring the
reduction in volume of a chamber using an ultrasound. These methods
of sensing the onset of a contraction may have a delay between the
actual onset of the contraction and the sensing of an onset of
contraction.
In some embodiments, the AV valve may be closed after the onset of
contraction of at least one atrium. For example, the AV valve may
be closed about 0 ms to about 70 ms after the onset of contraction
of at least one atrium. In some embodiments, the AV valve may be
closed about 0 ms to about 40 ms after the onset of contraction of
at least one atrium. In some embodiments, the AV valve may be
closed about 0 ms to about 10 ms after the onset of contraction of
at least one atrium. In some embodiments, the AV valve may be
closed about 0 ms to about 5 ms after the onset of contraction of
at least one atrium.
Typically, an atrial contraction may begin about 40 ms to about 100
ms after the onset of atrial excitation. In some embodiments, the
AV valve may be closed after the onset of atrial excitation. For
example, the AV valve may be closed about 40 ms to about 170 ms
after the onset of atrial excitation. For example, the AV valve may
be closed about 40 ms to about 110 ms after the onset of atrial
excitation. In another embodiment, the AV valve may be closed about
40 ms to about 80 ms after the onset of atrial excitation. For
example, the AV valve may be closed about 40 ms to about 75 ms
after the onset of atrial excitation. For example, the AV valve may
be closed about 40 ms to about 50 ms after the onset of atrial
excitation.
In some embodiments, the onset of excitation in a chamber may be
sensed and a stimulation pulse may be timed relative to the sensed
onset of excitation. The onset of excitation is the initiation of a
propagating action potential through a chamber. The onset of
excitation may be sensed by sensing the local electrical activity
of a chamber using a sensing electrode connected to an amplifier.
The onset of excitation can also be detected by
electrocardiography.
In some embodiments, methods of sensing the onset of excitation may
have a delay between the actual onset of the excitation and the
sensing of an onset of excitation. The timing of a sensed atrial
excitation may be determined by taking into account the delay
between actual onset of excitation and the sensing thereof. For
example, if a sensing delay is estimated to be 20-40 ms, and
stimulation pulses are to be delivered 0-70 ms after onset of
atrial excitation, a system may be set to deliver pulses between 40
ms before the next anticipated sensing event to 30 ms after the
next anticipated sensing event or 30 ms after the next sensing
event. Likewise, if the stimulation pulses are to be delivered to
the ventricle 0-50 ms before onset of atrial excitation, assuming
the same 20-40 ms sensing delay, a system may be set to deliver
pulses between 40 ms before the next anticipated sensing event to
90 ms before the next anticipated sensing event. Sensing delays may
be due to one or more of a distance between the site of onset of
excitation and a sensing electrode, the level of the electrical
signal, characteristics of the sensing circuit, and the threshold
set of a sensing event. The delay may include, for example, the
duration of the signal propagation from the origin of excitation to
the electrode location, the duration related to the frequency
response of the sensing circuit, and/or the duration necessary for
the signal propagation energy to reach a level detectable by a
sensing circuit. The delay may be significant and can range, for
example, between about 5 ms to about 100 ms. One approach for
estimating the delay is to use the time difference between an AV
delay measured when both atrium and ventricle are sensed and the AV
delay when the atrium is paced and the ventricle is sensed. Other
approaches may use calculation of the amplifier response time based
on the set threshold, signal strength, and frequency content. Other
approaches may include modifying the delay used with atrial sensing
until the effect on blood pressure is the same as the effect
obtained by pacing both atrium and ventricle with the desired AV
delay.
In some embodiments, the AV valve may be closed before the onset of
excitation or contraction of at least one atrium. For example, the
AV valve may be closed within about 0 ms to about 5 ms before the
onset of excitation or contraction of at least one atrium. In some
embodiments, the AV valve may be closed at the same time as the
onset of excitation or contraction of at least one atrium.
In some embodiments, direct mechanical control of AV valve closure
may be performed. In such embodiments, a mechanical device or a
portion thereof may be implanted in the patient, and operated to
cause the closing of a valve between the atrium and ventricle. For
example, an artificial valve may be implanted in the patient's
heart and operated to close mechanically in accordance with some
embodiments. In such embodiments, instead of or in addition to
providing a stimulation pattern, the aforementioned closure of the
AV valves may be accomplished by controlling the functioning of the
implanted valve.
In some embodiments, a shortened or even negative time interval
between the onset of atrial excitation and ventricular excitation
is employed to reduce cardiac filling, thereby reducing blood
pressure. As used herein, a negative time interval between the
onsets of atrial excitation and ventricular excitation means that
in a single cardiac cycle, the onset of excitation for the at least
one ventricle occurs before the onset of atrial excitation. In this
case, atrial contraction may take place, at least partially,
against a closed AV valve, since the generated pressure in the
ventricles may be greater than the pressure in the atria. A short
time after the initiation of ventricular contraction, the pressure
in the ventricles may exceed the pressure in the atria and may
result in the passive closure of the valve. This closure of the
valve may reduce or even obliterate the atrial kick and, in turn,
reduce ventricular filling. Consequently, the force of ventricular
contraction may be reduced and blood pressure may drop.
The time between the start of excitation and the start of the
mechanical contraction in each cardiac chamber is not fixed. Thus,
the timing of excitation does not guarantee the same effect on the
timing between contractions. However, in some embodiments, the
timing between excitations is used as a frame of reference for
practical reasons. The ultimate purpose of controlling the timing
of excitation is to control the timing of a contraction.
In some embodiments, a shortened or even negative time interval
between the onset of atrial contraction and ventricular contraction
may be employed to reduce cardiac filling, thereby reducing blood
pressure. In this case, better control over the contribution of the
atria may be obtained since the start of the contraction of the
ventricle will result with the closure of the valve.
In some embodiments, 40% or more of an atrial contraction may occur
during ventricular systole. For example, the atrial contraction may
start approximately 60 ms or less before the contraction of the
ventricle, or the excitation of the atria may occur 60 ms or less
before the excitation of the ventricle. In some embodiments 80% or
more of an atrial contraction may occur during ventricular systole.
For example, the contraction may start approximately 20 ms or less
before the contraction of the ventricle, or the excitation of the
atria may occur 20 ms or less before the excitation of the
ventricle. In some embodiments, 100% of an atrial contraction may
occur during ventricular systole, in which case ventricle
excitation is timed such that ventricle contraction will begin
before the commencement of atrial contraction. This may include
exciting the ventricle before the onset of atrial excitation.
Some embodiments provide a method for causing the contraction of at
least one ventricle of a heart, such that the at least one
ventricle contracts during or before the contraction of the
corresponding atrium. One way to achieve this goal is by exciting
the ventricle at a point in time between about 50 ms before to
about 70 ms after the onset of excitation of the corresponding
atrium. In some embodiments, the time interval between the onset of
excitation of at least one ventricle and the onset of excitation of
the corresponding atrium may be zero. In other words, the onset of
excitation for the at least one ventricle may occur at the same
time as the onset of excitation of the corresponding atrium. In
some embodiments, the onset of excitation of the ventricle may
occur between about 0 ms to about 50 ms before the onset of atrial
excitation. In some embodiments, the onset of excitation of the
ventricle may occur at least 2 ms before to at least 2 ms after the
onset of excitation of the at least one atrium. In some
embodiments, the onset of excitation of the ventricle may occur at
least 10 ms before to at least 10 ms after the onset of excitation
of the at least one atrium. In some embodiments, the onset of
excitation of the ventricle may occur at least 20 ms before to at
least 20 ms after the onset of excitation of the at least one
atrium. In some embodiments, the onset of excitation of the
ventricle may occur at least 40 ms before to at least 40 ms after
the onset of excitation of the at least one atrium.
In some embodiments, a method may comprise delivering a stimulation
pulse from a stimulation circuit to at least one of an atrium and a
ventricle, and operating a processor circuit coupled to the
stimulation circuit to operate in an operating mode in which a
ventricle is stimulated to cause ventricular excitation to commence
between about 0 ms and about 50 ms before the onset of atrial
excitation in at least one atrium, thereby reducing the ventricular
filling volume from the pretreatment ventricular filling volume and
reducing the patient's blood pressure from the pretreatment blood
pressure. In such embodiments, atrial excitation may be sensed to
determine the onset of atrial excitation. The time interval between
the onset of atrial excitation and the moment that atrial
excitation is sensed may be known and used to calculate the timing
of the onset of atrial excitation. For example, if it is known that
atrial excitation is sensed 20 ms after the onset of atrial
excitation and the ventricle is to be stimulated 40 ms before the
onset of atrial excitation, then the ventricle is to be stimulated
60 ms before the anticipated sensing of atrial excitation. In other
embodiments, the method may comprise operating a processor circuit
coupled to the stimulation circuit to operate in an operating mode
in which an atrium is stimulated to cause atrial excitation to
commence between about 0 ms and about 50 ms after the onset of
ventricular excitation in at least one ventricle, thereby reducing
the ventricular filling volume from the pretreatment ventricular
filling volume and reducing the patient's blood pressure from the
pretreatment blood pressure. For example, the processor circuit may
be configured to operate in an operating mode in which one or more
excitatory pulses are delivered to an atrium between about 0 ms and
about 50 ms after one or more excitatory pulses are provided to the
patient's ventricle. In such embodiments, the pacing may be timed
without relying on sensing atrial excitation. Optionally, in such
embodiments, atrial excitation is sensed in order to confirm that
one or more excitatory pulses are delivered to an atrium before a
natural excitation takes place. Optionally, atrial excitation is
set to commence between about 0 ms and about 50 ms after the onset
of ventricular excitation when the intrinsic atrial excitation rate
is lower than the intrinsic ventricular excitation rate.
In some embodiments, a device may comprise a stimulation circuit
configured to deliver a stimulation pulse to at least one of an
atrium and a ventricle. The device may comprise a processor circuit
coupled to the stimulation circuit. In some embodiments, the
processor circuit may be configured to operate in an operating mode
in which a ventricle is stimulated to cause ventricular excitation
to commence between about 0 ms and about 50 ms before the onset of
atrial excitation in at least one atrium, thereby reducing the
ventricular filling volume from the pretreatment ventricular
filling volume and reducing the patient's blood pressure from the
pretreatment blood pressure. In such embodiments, atrial excitation
may be sensed to determine the onset of atrial excitation. The time
interval between the onset of atrial excitation and the moment that
atrial excitation is sensed may be known and used to calculate the
timing of the onset of atrial excitation. For example, if it is
known or estimated that atrial excitation is sensed 20 ms after the
onset of atrial excitation and the ventricle is to be stimulated 40
ms before the onset of atrial excitation, then the ventricle is to
be stimulated 60 ms before the anticipated sensing of atrial
excitation. In other embodiments, the processor circuit may be
configured to operate in an operating mode in which an atrium is
stimulated to cause atrial excitation to commence between about 0
ms and about 50 ms after the onset of ventricular excitation in at
least one ventricle, thereby reducing the ventricular filling
volume from the pretreatment ventricular filling volume and
reducing the patient's blood pressure from the pretreatment blood
pressure. For example, the processor circuit may be configured to
operate in an operating mode in which one or more excitatory pulses
are delivered to an atrium between about 0 ms and about 50 ms after
one or more excitatory pulses are provided to the patient's
ventricle. In such embodiments, the pacing may be timed without
relying on sensing atrial excitation. Optionally, in such
embodiments atrial excitation is sensed in order to confirm that
one or more excitatory pulses are delivered to an atrium before a
natural excitation takes place. Optionally, atrial excitation is
set to commence between about 0 ms and about 50 ms after the onset
of ventricular excitation when the intrinsic atrial excitation rate
is lower than the intrinsic ventricular excitation rate.
FIGS. 10A and 10B depict a healthy anesthetized canine heart,
showing an electrocardiogram (ECG), left ventricle pressure (LVP)
and arterial (blood) pressure (AP) traced over a period of time. In
FIG. 10A, before point 101, the heart was allowed to beat
naturally, and the ECG, LVP, and AP were traced. At point 101,
ventricular pacing commenced. The ventricle was paced 2 ms after
the onset of atrial excitation. This pacing caused an immediate
change in the ECG, which was concomitant with a reduction of both
LVP and AP. The pacing continued at a 2 ms time interval between
the onset of atrial contractions and the onset of ventricular
pacing until point 103 in FIG. 10B, where pacing ceased. As seen,
immediately upon cessation of pacing, the ECG, LVP, and BP all
returned essentially to the same values as before pacing.
FIGS. 11A and 11B show a hypertensive canine heart under a natural
heartbeat (FIG. 11A) and when paced at a time interval of 2 ms
between the onset of atrial contractions and ventricular pacing
(FIG. 11B). Each of these figures shows traces of an ECG, right
ventricular pressure (RVP), a magnified portion of the RVP, and
right atrial pressure (RAP) of the heart.
In FIG. 11A, the P wave and QRS of the natural heartbeat are
clearly seen. An increase in atrial pressure is seen following the
P wave as a result of atrial contraction. In the RVP trace, a sharp
increase in RVP is seen following a QRS complex on the ECG. This is
a manifestation of ventricular contraction. When observed at a
higher magnification, this sharp increase in RVP is preceded by an
earlier, smaller increase in RVP, which coincides with atrial
contraction and a reduction in atrial pressure and is a result of
blood emptying from the atrium into the chamber. This is the atrial
kick. In FIG. 11B, where pacing is at a time interval of 2 ms, the
P wave is essentially unnoticeable on the ECG, and an artifact of
the electrical stimulator is discernible. The atrial kick in this
case is not visible on the magnified trace of right ventricular
pressure because the atrial contraction occurred at the same time
or even a little after the start of ventricular contraction.
In FIG. 12, a hypertensive canine heart was paced either at a time
interval of 60 ms between the pacing of the atria and the pacing of
the ventricle (trace portions 105 and 107) or a time interval 120
ms of between atrial and ventricular pacing (trace portion 109).
The trace shows the ECG of the heart, left ventricular pressure
(LVP), right ventricular pressure (RVP), a magnification of RVP,
and right atrial pressure (RAP). As seen in trace portions of RVP
magnified corresponding with trace portions 105 and 107, the atrial
kick during pacing at the 60 ms time interval is very slight and
the contraction of the ventricle begins slightly after the peak of
atrial contraction. In this case the contribution of atrial kick to
ventricular filling is markedly reduced but not totally eliminated
and, on the other end, the peak of atrial contraction does not
occur against a closed valve and atrial stretch does not increase.
During pacing at a time interval of 120 ms, the atrial kick is
clearly seen (portion 109 in trace RVP magnified), but the start of
the ventricular contraction and the closure of the AV valve occur
before the completion of atrial contraction, thereby slightly
reducing the contribution of the atrial kick to ventricular
filling.
In FIG. 16, the heart of a hypertensive patient was paced with
different AV delays. This example shows the results obtained by
pacing in both an atrium and a corresponding ventricle versus
pacing only the ventricle based on the sensed pulses in the atrium.
During interval d-d', atrial pulses were sensed and ventricular
pulses were paced with an AV delay of 2 ms. During interval e-e',
the atrium and ventricle were both paced with an AV delay of 2 ms.
During interval f-f', the atrium and the ventricle were both paced
with an AV delay of 40 ms. During interval g-g', the atrium and the
ventricle were both paced with an AV delay of 20 ms. During
interval h-h', the atrium and the ventricle were both paced with an
AV delay of 80 ms. As shown in this example, when comparing
interval d-d' with interval e-e', the blood pressure is reduced
more when the atrium is paced during interval e-e' than when atrial
activity was just sensed. As also shown in this example, when
comparing interval e-e', interval f-f', interval g-g', and interval
h-h', the shorter AV delays caused more of a reduction in blood
pressure than the longer ones. For example, interval g-g' (20 ms
AV-delay) shows a higher blood pressure than interval e-e' (2 ms
AV-delay). As shown from the results of this example, the changes
in blood pressure may be caused at least partially by the different
AV delays, which result in different percentages of atrial
contraction against a closed valve.
Exemplary Embodiments of Methods for Reducing Atrial Kick
An exemplary method 40 for reducing blood pressure is depicted
schematically in FIG. 13. Method 40 may be performed by device 50
of FIG. 14, described below. Accordingly, device 50 may be
configured to perform any or all steps of method 40. Similarly,
method 40 may include any steps device 50 is configured to perform.
For example, method 40 may include any of the functions discussed
above with respect to device 50. Method 40 may include any steps
from method 600. Similarly, method 600 may include any steps from
method 40. Method 40 may include any steps that system 700 may be
configured to perform. System 700 may be configured to perform any
or all steps of method 40.
In some embodiments, method 40 may include a step 41 of atrial
excitation. In some embodiments, step 41 includes sensing an atrial
excitation. For example, step 41 may include sensing an intrinsic
atrial excitation. In some embodiments, step 41 includes triggering
atrial excitation. Method 40 may include a step 42 in which a time
interval is applied. Method 40 may include a step 43 of triggering
AV valve closure. In some embodiments, step 43 may be performed by
applying an excitatory current to the at least one ventricle and/or
by actuating an artificial valve between the at least one atrium
and the corresponding ventricle(s) to close. In some embodiments,
step 41, step 42, and step 43 may be repeated as depicted by a
return arrow leading back to step 41 from step 43. In some
embodiments, an excitatory current may be applied to both
ventricles, at the same time or in sequence. In some embodiments,
where both ventricles are paced in sequence, the time interval may
be measured between the onset of excitation of at least one atrium
(e.g., the right atrium) and the onset of excitation of the
corresponding ventricle to be paced (e.g., the right ventricle). In
some embodiments, where the time interval is set to be zero or
negative, step 43 may be performed before or at the same time as
step 41. In some embodiments, the time interval may be measured in
milliseconds.
Optionally, contraction of the atrium and the ventricle may be
caused by controlling both contractions (e.g. by controlling the
excitations leading to the contractions). Optionally, the onset of
excitation of the atrium is sensed, which sensing triggers the
closing of a valve at the prescribed timing interval. Optionally,
both atria are paced. In some embodiments, where both AV valves are
closed in sequence (e.g., as both ventricles are paced in
sequence), the timing interval is measured from the onset of
excitation of the first atrium to be paced and the onset of the
valve closing or the onset of excitation of at least one ventricle.
Optionally the timing of an excitation (e.g. the onset of
excitation) of one or more chambers is estimated, for example based
on the timing in one or more preceding heart cycles, and one or
more excitation stimuli are delivered to the same and/or to a
different chamber at a desired time interval before and/or after
the estimated timing.
In some embodiments, method 40 may be repeated for every heartbeat.
In some embodiments, method 40 may be performed intermittently. For
example, the method may be applied once every few heartbeats.
Alternatively, method 40 may be applied for a few heartbeats,
stopped for one or more heartbeats, and then applied again. For
example, method 40 may be applied for 5 to 15 heartbeats, stopped
for 2 to 5 heartbeats, and then resumed again. In some embodiments,
the pattern of application/avoiding application may be more complex
and may be optionally based on a predefined algorithm. For example,
an algorithm may adjust parameters of stimulation rather than
simply stop and start stimulation. Application of method 40 in some
embodiments reduces ventricle filling between heartbeats thereby
potentially reducing the ejection profile. As used herein, the
ejection profile of a heart is the total amount of blood pumped by
the heart in a given period of time. In some embodiments, an
intermittent application of method 40 may be applied to counteract
a reduction in the ejection profile of the heart.
In some embodiments, the time interval applied in step 42 may be
selected based on feedback. In such cases, method 40 may include
step 44 of sensing a feedback parameter from one or more of the
heart chambers, any portion thereof, and/or the body of the
patient. For example, feedback information may be obtained by
monitoring directly or indirectly one or more of the atrial kick,
blood pressure (e.g., at an artery), ventricular pressure, and/or
atrial pressure. In some embodiments, feedback information may
additionally or alternatively include the degree of overlap between
the time when the atrium contracts and the time when the AV valve
is closed and/or the time when the ventricle contracts. For
example, an ultrasound sensor may be used to detect cardiac
activity, for example, by ultrasound imaging of cardiac activity or
by creating an echocardiogram (ECHO). In some embodiments, step 44
may include using an ultrasound sensor to detect the flow of blood
(e.g., the velocity of flow) and/or cardiac tissue movement at any
arbitrary point using pulsed or continuous wave Doppler ultrasound.
Optionally, step 44 may include using an ultrasound sensor to
detect an A wave corresponding to the contraction of the left
atrium and the flow of blood to the left ventricle.
Method may include a step 45 of adjusting the time interval from
step 42 based on the feedback information from step 44. For
example, step 45 may include adjusting the time interval based on a
sensed blood pressure. As shown by the arrow directed from step 45
to step 41 in FIG. 13, step 41, step 42, step 43, and/or step 44
may be repeated after performing step 45. In some embodiments, the
time interval may be initially set at a first value during step 41
and, based on feedback sensing performed during step 44, the time
interval may be reduced or increased during step 45 until the
feedback value is within a given range (or above or below a given
value). For example, the time interval may be adjusted until such
time that systolic blood pressure is above 100 mmHg and/or below
140 mmHg and/or diastolic blood pressure is below 90 mmHg and/or
above 60 mmHg.
In some embodiments, step 44 and step 45 may be performed during
operation of method 40 for every application of step 43 (e.g.,
application of a ventricular pacing stimulus). In some embodiments,
alternatively or additionally, step 44 and step 45 may be performed
upon providing a device to a patient (e.g., by implantation of the
device) according to one or more embodiments. The adjusting steps
may be repeated periodically (for example by a care taker during a
checkup) and/or intermittently (for example once an hour or once
every few applications of a ventricular pacing stimulus). In some
embodiments, step 45 may be performed when feedback information
indicates that one or more sensed parameters exceed a preset range
for a period of time that exceeds a predefined period.
The steps of method 40 may be performed in any order. For example,
the steps may be performed in the order indicated by the arrows
shown in FIG. 13. In another embodiment, step 42 may be performed
before step 41.
The timing of atrial contraction, atrial excitation, ventricular
contraction, closing and/or opening of the AV valve(s), and/or the
flow or lack thereof of blood from one or more atria to the
respective ventricle(s) and/or blood pressure may be detected by
any method known in the art and may be used as feedback control. In
some embodiments, the onset of excitation may be used as a trigger
for the delivery of an excitatory stimulus to one or more
ventricles. The sensed information may be additionally or
alternatively be used in the adjusting of a timing interval of the
device.
Optionally, feedback parameters may allow responding to conditions
that require additional throughput from the heart, and rather than
adjust the timing interval they may be used to automatically stop
the causing of valve closing at a shortened timing interval. For
example, the feedback parameters may lead to an adjustment during
exercise. In this example, a heart rate sensor may be used to
provide feedback information on the heart rate of the patient. If
the heart rate is above a given threshold the feedback may be used
to cause the device to stop. The device may be activated again
based on sensed feedback information, for example, when the heart
rate is below a given threshold and/or after a predetermined period
has passed.
Embodiments of Devices for Reducing Blood Pressure
Attention is now drawn to FIG. 14, which schematically depicts an
exemplary device 50 according to an embodiment. Device 50 may be
constructed and have components similar to a cardiac pacemaker
essentially as known in the art with some modifications as
discussed herein. Optionally, the device is implantable.
Optionally, the device comprises components that may provide
additional and/or alternative electrical treatments of the heart
(e.g., defibrillation). Device 50 may be configured for
implantation in the body of a patient essentially as is known in
the art for implantable pacemakers, optionally with some
modifications as discussed herein. Device 50 may include any
components of system 700 and system 700 may include any components
of device 50.
Device 50 may include a biocompatible body 51, one or more
controllers 52, a power source 53, and a telemetry unit 56. Body 51
may comprise a housing for encasing a plurality of components of
the device. Controller(s) 52 may be configured to control the
operation of the device. For example, controller(s) 52 may control
the delivery of stimulation pulses. In some embodiments, power
source 53 may include a battery. For example, power source 53 may
include a rechargeable battery. In some embodiments, power source
53 may include a battery that is rechargeable by induction. In some
embodiments, telemetry unit 56 may be configured to communicate
with one or more other units and/or components. For example,
telemetry unit 56 may be configured to communicate with an external
programmer and/or a receiving unit for receiving data recorded on
device 50 during operation.
In some embodiments, device 50 may be configured to be attached to
one or more electrodes and/or sensors. The electrodes and/or
sensors may be integrated in device 50, attached thereto, and/or
connectable therewith. In some embodiments, the electrodes may
include ventricular electrode(s) 561 configured to pace at least
one ventricle. Additionally or alternatively, the device may be
connected, optionally via wires or wirelessly, to at least one
implanted artificial valve 562. Additionally, device 50 may
comprise one or more atrial electrode(s) 57 for pacing one or more
atria, and/or one or more atrial sensors 58 for sensing the onset
of atrial excitation, and/or one or more sensors 59 for providing
other feedback parameters.
In some embodiments, sensor(s) 59 may comprise one or more pressure
sensors, electrical sensors (e.g., ECG monitoring), flow sensors,
heart rate sensors, activity sensors, and/or volume sensors.
Sensor(s) 59 may include mechanical sensors and/or electronic
sensors (e.g., ultrasound sensors, electrodes, and/or RF
transceivers). In some embodiments, sensor(s) 59 may communicate
with device 50 via telemetry.
In some embodiments, ventricular electrode(s) 561 and/or atrial
electrode(s) 57 may be standard pacing electrodes. Ventricular
electrode(s) 561 may be positioned relative to the heart at
positions as known in the art for ventricular pacing. For example,
ventricular electrode(s) may be placed in and/or near one or more
of the ventricles. In some embodiments, atrial electrode(s) 57 may
be placed in and/or near one or more of the atria. In some
embodiments, atrial electrode(s) 57 may be attached to the one or
more atria at one or more positions selected to provide early
detection of atrial excitation or depolarization. For example, in
some embodiments, atrial electrode(s) 57 may be attached to the
right atrium near the site of the sinoatrial (SA) node.
One position of ventricular electrode(s) 561 may be such that
pacing may reduce or minimize the prolongation of QRS when the
heart is paced, to reduce or even minimize dyssynchrony. In some
embodiments, this position is on the ventricular septum near the
Bundle of His. Ventricular electrode(s) 561 may additionally or
alternatively be placed on the epicardium of the heart or in
coronary veins. More than one electrode can be placed on the
ventricles to provide biventricular pacing, optionally to reduce
dyssynchrony.
Device 50 may include a pulse generator, or stimulation circuit,
configured to deliver a stimulation pulse to at least one cardiac
chamber. The pulse generator, or stimulation circuit, may include
some or all standard capabilities of a conventional pacemaker.
Controller 52 may be configured to control the pulse generator, or
stimulation circuit. Atrial sensor(s) 58 (and optionally other
electrode sensors configured to sense other heart chambers) may be
connected to device 50 via specific circuits that will amplify the
electrical activity of the heart and allow sampling and detection
of the activation of the specific chamber. Other circuits may be
configured to deliver stimulation to a specific electrode to pace
the heart, creating propagating electrical activation.
In some embodiments, one or more additional sensors 59 may be
placed in and/or on one or more of the atria and/or in and/or on
one or more of the ventricles and/or in and/or on one or more other
locations that might optionally be adjacent the heart. For example,
one or more sensors may be placed on and/or in vena cava and/or on
one or more arteries and/or within one or more cardiac chambers.
These sensors may measure pressure, or other indicators, such as,
for example, impedance and/or flow.
In some embodiments, controller 52 may comprise or be a
microprocessor powered by power source 53. In some embodiments,
device 50 may comprise a clock 54, for example, generated by a
crystal. Device 50 may comprise an internal memory 55 and/or be
connected to external memory. For example, device may connect to an
external memory via telemetry unit 56. In some embodiments,
telemetry unit 56 may be configured to allow communication with
external devices such as a programmer and/or one or more of sensors
59. Any and all feedback information and/or a log of device
operation may be stored in internal memory 55 and/or relayed by
telemetry unit 56 to an external memory unit.
In some embodiments, controller 52 may operate in accordance with
at least one embodiment of a method described herein.
In some embodiments, device 50 may comprise one or more sensors for
sensing one or more feedback parameters to control the application
of the AV delay and/or its magnitude.
Embodiments of Artificial Valves
Additionally or alternatively, device 50 may be configured to
directly control the operation of at least one implanted artificial
valve 562. Attention is now drawn to FIG. 15, which schematically
depicts an artificial valve 60 according to an embodiment of the
invention. Valve 60 as depicted in the example is a bi-leaflet,
essentially as known in the art for artificial valves. While the
following example relates to a bi-leaflet valve it is appreciated
that embodiments may be implemented in other artificial valves, for
example, caged ball valves and disc valves as well.
As shown in FIG. 15, valve 60 may comprise a ring 61 for suturing
the valve in place when implanted in a heart of a patient. Valve 60
may include two semicircular leaflets 62 that rotate about struts
63 attached to ring 61. In this schematic representation, other
device components are schematically depicted as body 64, which
corresponds to body 51 as shown in FIG. 14. Body 64 may receive
feedback information from heart 65, in which valve 60 is
implanted.
Valve 60 differs from conventional artificial valves in that its
closure may be directly controlled by device 50. Valve 60 may
comprise a mechanism (for example, a coil or a hydraulic mechanism)
that is configured to actively cause closure of the valve (for
example, by rotating struts 63 or by inflating a portion of the one
or more of leaflets 62). The mechanism may later be brought back to
a relaxed position to allow opening of the valve and to allow its
repeated closing as needed. The relaxation may be performed at a
predetermined time after closing. Additionally or alternatively,
relaxation may be affected in response to a sensor reading
ventricular activity (e.g., a pressure sensor). Control over valve
60 may be operated wirelessly (using a telemetry unit associated
with the valve) or by wired communication with components in body
64. In some embodiments, valve 60 may be a valve configured to be
opened and closed independent of fluid pressure acting on the
valve. For example, valve 60 may be a ball valve.
Effects of Embodiments for Reducing Blood Pressure
Overall, some embodiments of the disclosed methods and systems
provide different approaches to reducing the filling of at least
one ventricle, consequently reducing blood pressure. Unlike
previous mechanical methods for reducing blood pressure, some
embodiments described herein may achieve this goal without
increasing pressure within the at least one corresponding atrium.
Without an increase in atrial pressure to trigger the secretion of
atrial natriuretic hormone, or atrial natriuretic peptide, the
reduction of blood pressure can be mechanically controlled. The
disclosed embodiments may prevent an unwanted effect on heart rate
and may reduce the likelihood of canon atrial waves.
Some of the disclosed embodiments may reduce atrial kick while also
increasing atrial stretch, causing the release of atrial
natriuretic peptide. For example, disclosed embodiments may
comprise a method including a step of stimulating a heart to cause
an atrium thereof to contract while a heart valve associated with
the atrium is closed such that the contraction distends the atrium.
Reducing atrial kick and causing the release of atrial natriuretic
peptide at the same time may have a synergistic effect on lowering
blood pressure. In some embodiments, controlling the timing of
valve closure relative to atrial contraction may control the amount
one or more atria stretches.
Unlike previous pharmaceutical or mechanical methods for reducing
blood pressure, some of the disclosed embodiments achieve the goal
of reducing blood pressure immediately. For example, a reduction in
blood pressure may occur within 1-3 sec or within 1, 3, or 5
heartbeats of the application of electricity and the blood pressure
may reach a minimal blood pressure value within less than 5
heartbeats from the beginning of stimulation.
Examples discussed above strike a balance between mechanical
treatment, neuronal feedback, and the natural release of hormones
that cause adaptation. The mechanical treatment and the natural
release of hormones may be additive or even synergistic mechanisms.
The hormonal release affects the cardiovascular system while the
mechanical treatment affects the heart itself. Intermittently
delivering the mechanical treatment to reduce blood pressure may
affect both the neuronal and hormonal feedback controlling the
cardiovascular system and reduce adaptation.
The headings used in this specification are only meant to aid in
organization and do not define any terms.
The present disclosure is related to the following applications,
all of which are incorporated by reference in their entirety: U.S.
Patent Application Publication Number 2012/0215272 to Levin et al.,
published on Aug. 23, 2012; U.S. Patent Application Publication
Number 2011/0172731 to Levin et al., published on Jul. 14, 2011;
U.S. patent application Ser. No. 13/688,978 to Levin et al., filed
on Nov. 29, 2012; and U.S. Patent Application Publication Number
2012/0041502 to Schwartz et al., published on Feb. 16, 2012.
While various embodiments of the invention have been described, the
description is intended to be exemplary, rather than limiting and
it will be apparent to those of ordinary skill in the art that many
more embodiments and implementations are possible that are within
the scope of the invention. Accordingly, the invention is not to be
restricted except in light of the attached claims and their
equivalents. Also, various modifications and changes may be made
within the scope of the attached claims.
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